Blood plasma reduces symptoms and fatalities in outbreaks of coronavirus.
The US blood donation centers are making unarguable efforts to collect plasma from COVID-19 patients who have recovered from the disease. They are hoping to use it to save the life of those who are still infected with this disease.
According to the guidelines released on Tuesday by AABB, an international nonprofit agency focused on transfusion medicine and cellular therapies, many community blood centers located nationwide could be an important source for this Old treatment method known as Convalescent plasma therapy.
In this treatment method, Blood products are taking from patients who survived this viral disease, and it’s been injected into those that are still infected. This experimental practice has a history of been used in the 1930s to treat measles. In the 1918s, during the disastrous flu, recently, this plasma therapy has been used to treat those infected with H1N1 influenza, SARS and Ebola.
Clinical researches have shown that the use of plasma offers some hope and reduces symptoms and fatalities in past outbreaks of coronavirus.
In the recent surge of COVID-19, unproven evidence from china has shown that passive antibody treatment has helped COVID-19 patients until they were able to develop their natural antibodies that can fight off the disease.
This procedure is a promising one to try given that there’s no treatment or vaccine for COVID-19, experts say.
“There’s nothing else out there,” said Dr. Louis Katz, an expert in the blood industry, leading the AABB’s working group on Convalescent plasma.
The new guidelines were made a week later after the Federal Food and Drug Administration authorized the immediate use of Convalescent plasma by doctors for critically ill COVID-19 patients.
The first medical center to use this therapy is the Houston Methodist Hospital, and they have been able to treat two COVID-19 patients since Saturday, says a spokesman. The results are pending.
The New York blood center and some other sites have begun the collection of plasma since last week from patients who have recovered from this pandemic infection, and a few clinical trials have started to test this convalescent plasma for COVID-19. The American Red Cross has organized a site to collect information about potential plasma donors.
As the AABB join the effort with America’s Blood Centers, a new rollout could develop the practice exponentially, said Katz.
“This is all the medicine on the fly, right?” we don’t have the randomized controlled trials. We’re going to do our best that we can,” said Katz.
At community blood centers, the plasma will be collected from COVID-19 survivor donors with a lab-confirmed test; these donors must have tested negative and stopped experiencing symptoms for over 28days, according to the guidelines.
Several research laboratories and medical companies are trying effortlessly to detect the antibodies that fight the virus. It may be hard for some blood centers to access the test at first, says Katz.
Meanwhile, centers will be allowed to collect plasma from COVID-19 survivor donors, and it will be administered to “Critically ill patient as quickly a possible” and then test for antibody titers later, Said the FDA spokesman on Tuesday.
This will make a great difference in the potential amount of plasma collected from COVID-19 survivors. Said Katz. “We can go the whole hog, now that we have such an accommodating stance from the agency”, he also said.
Felberbaum noted that an emergency investigational new drug or e-IND, authorization is required to transfuse convalescent plasma into patients, but not to distribute it after collecting it from the donor. According to him, the FDA has granted “numerous” requests for emergency INDs and continues to grant them as they are received.
Seattle-area blood center, Bloodworks Northwest, is working effortlessly with the National institutes of health and the University of Washington to start harvesting plasma from victims who have recovered from COVID-19. These donations will become a part of a research study co-led by a professor of medicine, Dr. Terry Gernsheimer, at UW school of medicine. They will also be recorded in a national registry being created to track the result of the plasma therapy, says Dr. Rebecca Haley, a medical director of Bloodworks Bio that produces biological products.
There is a high expectancy of interest among those who have suffered through the global infection.
Dr. Jon Peters is a 66 years old family practice physician in Portland who is also a victim of the Pandemic infection. Although he’s at home and still experiencing symptoms, he plans to donate plasma and get back to work as soon as his symptoms subside and once he’s able to do so.
There is a very low-risk issue or complication for the donor but could be a lifesaver to someone out there, he said.
It is good to know that “at this point, they require every option they can get” hence, this therapy can offer a solution to this ravenous pandemic.
- Published in Blog
What is Exosome therapy?
Exosomes are extracellular vesicles (that’s particles that release naturally from a cell that cannot replicate) that are responsible for certain genetic information, otherwise known as Exosomes cell to cell communication. They transport molecules that are essential regulators of intracellular information between close and distant cells.
Exosomes play a vital role in the communication and rejuvenation of all the cells in our body. Despite not being a cell, Exosome has proven to be quite important in maintaining a healthy cellular terrain.
Exosomes are typically made by growing stem cells in culture. Taking the media where they grow and then getting rid of the stem cells. Due to the small size of Exosomes, the media is then ultra-centrifuged to concentrate the exosomes.
Exosomes contain different molecular constituents of their cell origin; these include proteins and RNA. Meanwhile, the Exosomal proteins composition varies with the cell and tissue of the origin; most Exsomes contains an evolutionarily conserved common set of protein molecules.
HOW TO ISOLATE EXOSOME FROM CULTURE STEM?
Exosomes can be isolated from culture stem cell using the method Ultracentrifugation. Often combined with sucrose density gradients, they float the relatively low-density Exosomes from other microvesicles. Cells and larger particles are removed by sequentially increasing the centrifugal forces. These procedures can take up to 30hours and requires an ultracentrifuge, extensive training and specialized equipment.
This method provides highly enriched exosomes but requires specialized training and equipment.
Now, this is how Exosomes works:
Exosomes carry genetic information. Protein and messenger RNA, they can relay this information, letting cells know when to and how to react. This Exosomes cell-to-cell communication is possible due to its unique shape and content.
Exosomes from young stem cells rejuvenate the older cells and assist in calming an overreactive immune system or modulating it to respond in a coordinated and more effective fashion.
WHAT IS EXOSOME THERAPY?
Exosome therapy is one of the hottest areas of regenerative medicine treatment. Researchers have given us valuable insight into the practical functionality of exosomes. While stem cells are usually responsible for the rejuvenation of older cells, they may not be able to supply all the information needed. So supporting Exosome function could have a greater positive effect, by providing a new piece of information to enhance the healing process.
Exosome therapy is a minimally invasive procedure commonly used in orthopedic injuries, for anti-aging and some other degenerative diseases. Exosomes treatment contains growth factors, messenger RNA, micro RNA, cytokines and other biologically active molecules in conjunction with stem cell therapy to speed up healing benefit.
Exosome therapy can be injected into the affected area like in orthopedic injuries or given intravenously for anti-aging.
This Exosome injection is administered directly into the affected area, and the dosing for every patient varies, and there is no set protocol.
Exosomes treatment is gaining popularity recently, due to its ability to transfer molecules from one cell to another via membrane vesicle, therefore influencing the immune system, such as dendrite cells and B cells.
What is exosome therapy used for?
HAIR LOSS: Exosomes injection can be used to regrow hair loss due to its growth factor content. When injected, Exosome will trigger healing, cell stimulation and natural regeneration of these hair follicles. Exosome hair loss therapy is cutting-edge in hair restoration. According to research, there is a positive relationship between Exosomes and Hair loss. Exosomes are ideal for people with thinning hair, excessive shedding or hair loss proper. This is because Exosomes are regenerative cells that can heal, repair, stimulate and restore cells and tissues.
LYME DISEASE: Exosomes may help to regulate processes in the body, and may also be beneficial to patients with Lyme disease. Lyme disease is a very complex disease, which compromises the immune system. Many Lyme patients suffer from dysfunction of the mast cells, increasing their inflammatory response and metabolic function. Incorporating Exosomes treatment in their treatment regimen may help break the inflammatory response and provide the body with necessary cellular information to facilitate healing.
ARTHRITIS: Arthritis as we all know, is the joint inflammation resulting from an autoimmune disease. Although various types of treatment are available to alleviate symptoms, no known therapy has been confirmed effective in reversing the disease progression.
In the field of regenerative medicine today, with the discovery of extracellular microvesicles, especially exosomes, many researchers have been able to offer a more exciting alternative on this subject matter. Exosome arthritis therapy is believed to play a more substantial role in bone and cartilage remodeling.
In a nutshell, Exosomes provides enormous potential in the field of regenerative medicine. You can advance your understanding of Exosomes and its relationship with stem cell in this course. This is an online-course https://www.cellulartherapycourse.com/ where physicians and medical personnel can get insight and deep understanding of this novel science (Exosome).
- Published in Blog
How to boost your immune system to fight cancer?
The human immune system helps to protect the body against illness and infection caused by bacteria, viruses, fungi, and parasites. This process is achieved by a collection of reactions and responses made by the body to damage these infected cells. It is also called immune responses.
This immune system is very crucial in cancer patients to help fight cancer, it dictates this cancer as abnormal and destroys it, but this is not enough to rid of cancer altogether. In most cases, cancer will weaken this immune system because it will spread into the bone marrow that produces blood cells that fights against infections and cause the bone marrow to decrease in its blood cell production.
When this immune system is unable to recognize these cells as abnormal, cellular growth will occur, causing uncontrolled growth and division of cells, that will, in turn, lead to cancer.
Cancer has been a serious and sensitive talk for both patients and doctors. Being diagnosed with cancer is frightening and tormenting, but due to the latest treatment method, recovering from this disease is increasingly possible. Living with cancer often brings an initial psychological crisis, but surprisingly it does not only affect you but your family and others close to you.
Cancers, especially genetic cancer can’t be prevented, so it is essential to be proactive about your health. If you’re diagnosed with cancer, some individual lifestyles that will help improve your cancer care, which includes managing stress. Reducing your stress level can help you to maintain physical and mental stress; you can use relaxation techniques such as meditation and yoga. Getting enough sleep is also crucial for patients living with cancer; this will help improve their health, mood, and coping ability. Also, it is best the limit their exposure to toxins that can increase one’s risk of being exposed to other deadly diseases.
A healthy feeding habit is critically important and can help manage cancer side effects, improve health, and quick recovery. Some tips to help you develop a good and healthy feeding diet include:
- Consuming assorted types of vegetables in all your meals. Vegetables are essential and should not just be a side dish but the centerpiece of your meal.
- Consuming foods rich in fiber like grains, beans, peas, nuts, and seeds.
- Consuming less red meat, like pork, lamb, goat, and bison.
- The presence of probiotic and prebiotic foods helps to support a healthy gut. Probiotic foods include yogurt or other fermented vegetables, and prebiotic foods include raw or cooked onions, dandelion greens, and legumes.
- Avoid processed and canned foods
- Avoid foods high in calories and low in nutrients like fruit-flavored drinks, sodas, candies, and sweets.
- Lastly, cut down on the excessive intake of alcohol.
Some other routines can help improve cancer care like regular exercise. Regular exercise helps to control fatigue, muscle tension, and anxiety in those with cancer, and it is essential, especially during and after cancer treatment, so keep fit and avoid adding unnecessary weight.
CANCER TREATMENT
There are many cancer treatment options for different types of cancers. Cancer treatments depend on the type and how to advance it is. Some patients with cancer will only have one treatment option, while others will end up with a combination of more that one treatments technique depending on the type and stage of cancer.
Curing cancer is one of the significant challenges of the 21st century. However, few advances to tame the immune system are getting closer to a future where cancer can be a curable disease.
Although cancer treatment is dependent on the stage and type, we need a wide range of therapies that work on cellular level like NK cell and stem cell therapies, wide enough to cover the whole spectrum of cancer. Cancer therapies involving the immune system is believed to be a milestone for cancer treatment advances, and the development of multiple immune cells as a therapeutic tool.
Our knowledge of cancer has dramatically improved in recent years. And it seems increasingly evident that there has been a surge of new technologies, and these technologies could make a great impact on the way we treat cancer, taking us closer to finally curing this deadly disease.
One of these promising cancer treatment advances is the natural killer (NK) cell-based immunotherapy.
NK CELLS
Natural killer cells have emerged as the newest promising therapeutic approach to cancer. Our understanding of the biological processes that take place in cancer is increasing rapidly, leading to this new type of targeted treatment and therapeutic approach. It is hard to overstate the possible importance of NK cells in the future of cancer. Modern researches have shown that NK cells are a type of treatment that stimulates a persons’ immune system to fight cancer, and this may give room for a greater number of chances to beat cancer for good. NK cells are also known for their ability to target cancer stem cells making these cancer stem cells visible to the immune system.
NK cells was first identified in the 1970s as a unique lymphocyte subset that can recognize and kill abnormal cells without prior sensitization of specific tumor antigen, thus preventing the growth of many cancers. During the late 1980s, something was observed, and this was that NK cells could destroy a lymphoma cell line that had lost MHC class I surface molecules while the original MHC class I+ cells were resistant to lysis, which led to the formation of the “missing self-hypothesis” which states that NK cells can sense the absence of “self” MHC class-I molecule on target cells. In recent years, the hypothesis was confirmed by the inhibitory and activating NK cell receptors.
This discovery indicates that autologous cells are not killed by NK cells, thanks to an appropriate expression of all self-HLA alleles, do not kill an autologous cell. In contrast, a wide spec of cancer types can be killed due to the loss of HLA molecules and to the expression/overexpression of ligands for NK cell activating receptors.
Now, this is how NK therapy works
NK cells firsts recognize the tumor cells via stress or danger signals from their sensors.
Then, the Activated NK cells directly decimate the target tumor cells through at least four mechanisms. These mechanisms are cytoplasmic granule release, death receptor-induced apoptosis, effector molecule production, or ADCC.
Furthermore, NK cells act as regulatory cells when reciprocally interact with DCs to improve their antigen uptake and presentation. This action helps in facilitating the generation of antigen-specific CTL responses that is vital in dictating foreign invasion and tumor cells.
Also, by producing cytokines such as IFN-γ, activated NK cells induce CD8+ T cells to become CTLs. Activated NK cells can also help in the differentiation of CD4+ T cells toward a Th1 response and promote CTL differentiation. Cytokines produced by NK cells might even have the unique ability to regulate antitumor cells, making them more proactive.
Accordingly, The cytokine gene transfer approach induces NK cell proliferation, and this increases survival capacity. Further enhancing their activation and also making them more potent in malignant cell multiplication dictation.
The NK cell scientist has assured that by using NK cell lines, modifying genes such as IL-2, IL-12, IL-15, and stem cell factor (SCF). They have been demonstrated the ability of the NK to restore their cytotoxic capacity as well as increase their proliferative rate, survival ability, and in vivo antitumor activity. However, the specificity of NK cells is still limited, and studies are even passing through phases. The approach focuses on retargeting NK cells to tumor cells by gene transfer of chimeric tumor-antigen specific receptors.
NK therapy is promising research; it raises the prospect of “one-end-solution” to many different types of cancers across the Globe. If the studies and experiments work out pretty well, the NK cells will be able to increase the activity of CD4+, CD19, and other important disease-fighting cells of the body.
There is no doubt that this an unimaginable feat, both in advancing our basic knowledge about regenerative medicine and for the possibility of future cancer treatment advances.
- Published in Blog
Can Stem Cells treatment Regrow the knee cartilage?
Some people believe that stem cell does all of this but studies have shown that It’s unlikely only in a few unique cases. You can observe minimal growth a year after the patient took treatment, but this doesn’t mean replacement of the cartilage.
The cartilage has a reduced regenerative capacity, and current and present pharmacological medications only offer symptomatic pain relief. Osteoarthritis patients that respond poorly to conventional therapies are ultimately treated with surgical procedures to promote cartilage repair by implantation of artificial joint structures (arthroplasty) or total joint replacement (TJR). Surgery has been the last resort for serious cartilage problems.
In the last two decades, stem cells derived from various tissues with varying differentiation and tissue regeneration potential have been used for the treatment of osteoarthritis, damage to bones and others either alone or in combination with natural or synthetic scaffolds. The stem cells derived from these tissues primarily aid cartilage repair. Although stem cells can be differentiated into chondrocytes in vitro or aid cartilage regeneration in vivo, their potential for Osteoarthritis management remains limited as cartilage regenerated by stem cells fails to fully recapitulate the structural and biomechanical properties of the native tissue. It isn’t easy for the cartilage to regrow and assume its original biomechanical and structure form.
Apparently, Due to the limited intrinsic capacity of resident chondrocytes to regrow the lost cartilage post-injury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair.
Also, stem cell-based therapies using mesenchyme stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in clinical and preclinical situations.
Part of the issues associated with Mesenchyme stem cells can be averted by using iPSCs. iPSCs are an ideal patient-specific unlimited cell source for autologous tissue regeneration. With the Promising in vitro; studies have shown that vitro results have already been demonstrated in the cartilage engineering field for iPSCs. These were generated from various cell types.
What Is Cartilage and How Does It Get Damaged?
Cartilage is a connective tissue in the human body and body of other animals. In our joints, we have a few kinds of cartilage, but most often people refer to the smooth lining of a joint called articular or hyaline cartilage. This kind of cartilage gives rise to a soft layer of cushion on the end of a bone at the joint. The cushion is essential for balance, mechanical functions and athletics. This tissue of the cartilage is very strong, yet it can compress, readjust and absorb varying degrees of energy. It is also very slippery, smooth and flexible and these features allow the joint to glide effortlessly through a broad range of physical motions of any kind.
When joint cartilage is not working correctly or damaged, this smooth-cushioning-layer can be worn away, and this becomes a problem. In the case of traumatic injuries, sometimes a sudden force causes the cartilage to break off or poorly become damaged, exposing the underlying bone of the body. In the case of osteoarthritis (also called degenerative/wear-and-tear arthritis), over time that smooth layer can wear thin and uneven. Aging can also cause the cartilage to break off and certain life factors and diseases too, e.g. autoimmune diseases.
Eventually, as that cushion of the bones wears away, joint movements can become inflexible, stiff and painful on one or both legs (bones). Joints can even become inflamed and swollen. And as all these conditions, typically causes pain and limitations in activity become problematic. The action or activities that involve these bones leads to crushing pain and discomfort, depending on the severity of the case. Almost all activities involve the movement of bones; hence this condition is not an easy one.
There are some treatments for cartilage damage and arthritis. Although there some medicines, most of these treatments are focused either on relieving symptoms by smoothing down the damaged cartilage or concentrate on replacing the joint surface with an artificial implant. The later is for end-stage conditions, and the artificial plane is procedures such as knee replacement or hip replacement surgery.
How Can Stem Cells Help?
Stem cells are specialized cells that can multiply reform and develop into different types of tissue. In the developmental stages of a fetus, stem cells are plentiful and surplus. However, in adulthood, stem cells are restricted to specific tasks of regenerating a few types of cells, such as blood cells and liver cells in some cases of damage. There are almost no stem cells found in cartilage tissue, and therefore there is little to no capacity to heal or regrow new cartilage. For adults, the ability to regrow new cartilage is even more difficult due to age and lack of stem cells in the cartilages.
Most often, in the setting of orthopedic surgery and joint problems, stem cells are obtained from adult stem cell sources. The primary sources are bone marrow and fatty tissue. These stem cells can develop into cartilage cells, called chondrocytes.
They also exhibit some other helpful qualities by stimulating the body to reduce inflammation, stimulate cell repair, and improve blood flow. This process is caused by the secretion of cellular signals and growth factors to stimulate the body to initiate healing processes.
Once stem cells have been obtained, they need to be delivered to the area of the cartilage that damaged. One option is to inject the stem cells into the joint. There have been many studies investigating just this, and some data shows improvement in symptoms. How much of this improvement is the result of new cartilage growth versus other effects of stem cells (the healing properties listed above, including the anti-inflammatory effects) is unknown.
There is a challenge with giving stem cell injection. The problem with just injecting stem cells is that cartilage is a complex tissue that is comprised of more than only cells hence this can pose a challenge because the stem can’t regenerate all the things in the cartilage.
To regrow the cartilage, the complex tissue structure and biomechanics of cartilage must also be reconstructed to its former status. Cartilage can often /described as having a scaffold-like structure that is composed of water, cells, collagen, and proteoglycans, and infection-fighting antibodies. Injecting just the stem cells is thought to be less effective in stimulating the formation of the entire cartilage structure hence the challenge.
Some studies are investigating the types of 3-dimensional tissue scaffolds engineered to have a cartilage-like structure. The stem can then be injected into the scaffold, in hopes of better restoring a healthy type of cartilage. Three-dimensional printing is becoming an exciting part of this type of research. If everything works out as expected, the cartilage reconstruction could be achieved to a very high percentage.
How do stem cells work?
Necessarily, stem cells are progenitor cells which are capable of regeneration and differentiation into a wide range of specialized cell types. Once injected, stem cells follow inflammatory signals from damaged tissues and have multiple ways of repairing these damaged areas. It works as though the part is developing new; like what is seen during a child’s development.
The mesenchyme stem cells (MSCs) we are using are considered to be multipotent (they can transform into different cell types but cannot form an organ) but not pluripotent. In the body, these cells Do NOT function by transforming into different cell types or tissues.
They act via anti-inflammatory activity, immune modulating capacity, and the ability to stimulate regeneration. We go through a very high thorough screening process to find cells that we know have the best anti-inflammatory activity, the best immune modulating capacity, and the best ability to stimulate regeneration process on the tissue with damage.
ISSCA (International Society for Stem Cells Applications) www.issca.us
This is a business located in Miami, FL, where people around the world come to take a certification in the newest Stem Cells Protocols.
Some organizations have put in efforts to help discover some solutions in stem medicine. International Society for Stem Cell Application (ISSCA ) is one of the leading associations in setting standards and promoting excellence in the field of Regenerative Medicine, researches, publications related education, certification, research and publications.
The ISSCA is a unique-multidisciplinary community of physicians, stem specialist and scientists with a mission to advance the science, technology and practice of Regenerative Medicine. Their aim is to treat disease and lessen human suffering. ISSCA generally advances the specialty of Regenerative Medicine and serves its members.
The ISSCA provides certifications and standards in the practice of Regenerative Medicine as a medical specialty.
Although the expectation on this stem cell course is yet to be achieved; however, this is a part of medicine that can offer one-end-solution to various bone and body problems.
With the recent high-tech studies, efforts and dynamics, stem cell treatment can be a breakthrough in the future as its perspectives are very promising and unique. It is also not dangerous on the long-run.
- Published in Blog
Clinical trials on NK cells give hope for many people Who are suffering from cancer.
Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. Pluripotent stem cells hold promise in the field of regenerative medicine. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic, and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease.
Natural killer cells are the type of cytotoxic lymphocyte critical to the innate immune system. The role NK cells play is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cells, acting at around three days after infection, and respond to tumor formation.
Typically, immune cells detect the major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release, causing apoptosis. NK cells are unique, however, as they can recognize stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction.
Clinical Trial on NK cells
In a first clinical trial, a natural killer cell immunotherapy derived from induced pluripotent stem cells is being tested for safety in 64 patients with a variety of solid tumors. The first subjects used for the study received the cells in February at the University of California, San Diego (UCSD) Moores Cancer Center and MD Anderson Cancer Center.
This study is targeting late-stage cancer patients with solid tumors, including lymphoma, colorectal cancer, and breast cancer. The FT500 NK cells do not undergo any further alterations and after their derivation from the induced pluripotent stem cells (iPSCs), offering the possibility of a quicker, ready-made treatment.
Human embryonic stem cells induced iPSCs
Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) provide an accessible, genetically tractable, and homogenous starting cell population to efficiently study human blood cell development. These cell populations provide platforms to develop new cell-based therapies to treat both malignant and nonmalignant hematological diseases.
The NK cells are immune cells in the same family as T and B cells and are very good at targeting cancer cells for destruction. Some Laboratory experiments have shown they do so by attacking cells that have lost their significant self-recognition signals that tell the immune system not to attack. This is the phenomenon that can happen among cancer cells but not to healthy cells. Experts are not sure how many cancer cells lose that signal. Researchers are hopeful that the clinical trial can help determine which cancer patients could benefit the most from NK cell treatment.
iPS Clone
The ability to induce pluripotent stem cells from committed, human somatic cells provides tremendous potential for regenerative medicine. However, there is a defined neoplastic potential inherent to such reprogramming that must be understood and may offer a model for critical understanding events in the formation of the tumor. Using genome-wide assays, we identify cancer-related epigenetic abnormalities that arise early during reprogramming and persist in induced pluripotent stem cell (iPS) clones. These include hundreds of abnormal gene silencing events, patterns of aberrant responses to epigenetic-modifying drugs resembling those for cancer cells, and presence in iPS and partially reprogrammed cells of cancer-specific gene promoter DNA methylation alterations.
Progress in adoptive T-cell therapy for cancer and infectious diseases is hampered by the lack of readily available antigen-specific, human T lymphocytes. Pluripotent stem cells could provide an estimable source of T lymphocytes, but the therapeutic potential of human pluripotent stem cell-derived lymphoid cells generated to date remains uncertain.
Modification of T cells
Recently, some Approved cell therapies for Cancer also rely on modifying T cells, in those cases to produce cancer cell–binding chimeric antigen receptors (CARs), and have been effective in treating certain cancers such as leukemia.
Application of CAR T-Cell Therapy in Solid tumours
The Car T technology has wowed the field by all but obliterating some patients’ blood cancers, but solid malignancies present new challenges.
Therapies that contains such chimeric antigen receptor (CAR) T cells have been approved for some types of so-called liquid cancers of the blood and bone marrow, large B-cell lymphoma and B-cell acute lymphoblastic leukemia. But the approach has not had as much success for solid tumors.
Serious research into the therapy for brain cancer started almost 20 years ago after cancer biologist WaldemarDebinski, then at Penn State, discovered that the receptor for the immune signaling molecule interleukin 13 (IL-13) was present on glioblastomas, but not on healthy brain tissue. The receptor thus seemed like an excellent target to home in on cancer cells while sparing healthy ones. The CAR spacer domain that spans the immune cells’ membranes and its intracellular co-stimulatory areas, as well as the process used to expand cells outside the body, to boost the T cells’ activity.
CAR T- A Safer Cell Therapy
While managing CAR T-cell therapy toxicity could help keep already-designed treatments on their march to the clinic, many immunotherapy companies are also working to develop a new generation of inherently safer therapies, yet just as efficient. A crucial part of achieving this goal will be improving CAR specificity for target cells. With current treatments, the destruction of normal cells is often an unavoidable side effect when healthy tissue carries the same antigens as tumors; noncancerous B cells, for example, are usually casualties in CD19-targeted therapies.
CAR T delivery is a non-easy factor in the treatment of solid tumors and other unknown forms of tumors. With the non-solid cancers, cells are administered by a blood infusion, and once in circulation, the CAR T can seek out and destroy the rogue cells. For solid tumors, it’s not so simple.
The main drawback of taking cells from a patient and developing them into a cellular immunotherapy product is that the process can take weeks.
Patel tells The Scientist “But for the majority of patients who may not be a candidate or may not have time to wait for such an approach, the idea that there’s off-the-shelf immunotherapy that could potentially as a living drug act against their cancer, I think is a fascinating concept,”
- Published in Blog
Stem cell treatment could offer one-end-solution to Diabetes
Insulin-producing cells grown in the lab could provide a possible cure for the age-long disease (diabetes).
Type 1 diabetes is an auto¬immune disease that wipes out insulin-producing pancreatic beta cells from the body and raises blood glucose to dangerously high levels. These high levels of Blood sugar level can be even fatal. Patients are being administered insulin and given other medications to maintain blood sugar level. To those who cannot maintain their blood sugar level, they are given beta-cell transplants but to tolerate beta cell transplants; patients have to take immunosuppressive drugs as well.
A report by a research group at Harvard University tells us that they used insulin-producing cells derived from human embryonic stem cells (ESCs) and induced pluripotent stem cells to lower blood glucose levels in mice. Nowadays, many laboratories are getting rapid progress in human stem cell technology to develop those cells that are functionally equivalent to beta-cells and the other pancreatic cell types. Other groups are developing novel biomaterials to encapsulate such cells and protect them against the immune system without the need for immunosuppressant.
Major pharmaceutical companies and life sciences venture capital firms have invested more than $100 million in each of the three most prominent biotechnological industries to bring such treatments into clinical use:
- Cambridge
- Massachusetts–based companies Semma Therapeutics
- Sigilon Therapeutics, and ViaCyte of San Diego
Researchers of UC San Francisco have transformed human stem cells into mature insulin-producing cells for the first time, a breakthrough in the effort to develop a cure for type-1 (T1) Diabetes. Replacing these cells, which are lost in patients with T1 diabetes, has long been a dream of regenerative medicine, but until now scientists had not been able to find out how to produce cells in a lab dish that work as they do in healthy adults.
What is T1 diabetes?
T1 diabetes is an autoimmune disorder that destroys the insulin-producing beta cells of the pancreas, typically in childhood. Without insulin’s ability to regulate glucose levels in the blood, spikes in blood sugar can cause severe organ damage and eventually death. The condition can be managed by taking regular shots of insulin with meals. However, people with type 1 diabetes still often experience serious health consequences like kidney failure, heart disease and stroke. Patients facing life-threatening complications of their condition may be eligible for a pancreas transplant from a deceased donor, but these are rare, and they are supposed to wait a long time.
Researchers have just made a breakthrough that might one day make these technologies obsolete, by transforming human stem cells into functional insulin-producing cells (also known as beta cells) – at least in mice.
“We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies,” explains one of the team, Matthias Hebrok from the University of California San Francisco (UCSF).
“This is a critical step towards our goal of creating cells that could be transplanted into patients with diabetes.”
Type-1 diabetes is characterized by a loss of insulin due to the immune system destroying cells in the pancreas – hence, type 1 diabetics need to introduce their insulin manually. Although this is a pretty good system, it’s not perfect.
Making insulin-producing cells from stem cells
Diabetes can be cured through an entire pancreas transplant or the transplantation of donor cells that produce insulin, but both of these options are limited because they rely on deceased donors. Scientists had already succeeded in turning stem cells into beta cells, but those cells remained stuck at an early stage in their maturity. That meant they weren’t responsive to blood glucose and weren’t able to secrete insulin in the right way.
Scientists at the University of California San Francisco made a breakthrough in the effort to cure diabetes mellitus type 1.
For the first time, researchers transformed human stem cells into mature insulin-producing cells, which could replace those lost in patients with the autoimmune. There is currently no known way to prevent type-1 (T1) diabetes, which destroys insulin production in the pancreas, limits glucose regulation, and results in high blood sugar levels. The condition can be managed with regular shots of insulin, but people with the disease often experience serious health complications like kidney failure, heart disease, and stroke.
“We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies,” according to Matthias Hebrok, senior author of a study published last week in the journal Nature Cell Biology.
“This is a critical step toward our goal of creating cells that could be transplanted into patients with diabetes,” Hebrok, director of the UCSF Diabetes Center, said in a statement.
Islets of Langerhans are groupings of cells that contain healthy beta cells, among others. As beta cells develop, they have to separate physically from the pancreas to form these islets.
The team artificially separated the pancreatic stem cells and regrouped them into these islet clusters. When they did this, the cells matured rapidly and become responsive to blood sugar. In fact, the islet clusters developed in ways “never before seen” in a lab. After producing these mature cells, the team transplanted them into mice. Within days, the cells were producing insulin similar to the islets in the mice. While the study has been successful in mice, it still needs to go through more rigorous testing to see if it would work for humans as well. But the research is up-and-coming. “We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies. This is a critical step towards our goal of creating cells that could be transplanted into patients with diabetes,” He said.
“We’re finally able to move forward on several different fronts that were previously closed to us,” he added. “The possibilities seem endless.”
Basic research keeps elucidating new aspects of beta cells; there seem to be several subtypes, so the gold standard for duplicating the cells is not entirely clear. Today, however, there is “a handful of groups in the world that can generate a cell that looks like a beta cell,” says Hebrok, who currently acts as scientific advisor to Semma and Sigilon, and has previously advised ViaCyte. “Certainly, companies have convinced themselves that what they have achieved is good enough to go into patients.”
The stem cell reprogramming methods that the three companies use to prompt cell differentiation create a mixture of islet cells. Beta cells sit in pancreatic islets of Langerhans alongside other types of endocrine cells. Alpha cells, for example, churn out glucagon, a hormone that stimulates the conversion of glycogen into glucose in the liver and raises blood sugar. Although the companies agree on the positive potential of islet cell mixtures, they take different approaches to developing and differentiating their cells. Semma, which was launched in 2014 to commercialize the Harvard group’s work and counts Novartis among its backers, describes its cells as fully mature, meaning that they are wholly differentiated into beta or other cells before transplantation. “Our cells are virtually indistinguishable from the ones you would isolate from donors,” says Semma chief executive officer BastianoSanna
To get around the donor problem, researchers, including the team at UCSF has been working on nudging stem cells into becoming fully-functional pancreatic beta cells for the last few years. Still, there have been some issues in getting them all the way there.
“The cells we and others were producing were getting stuck at an immature stage where they weren’t able to respond adequately to blood glucose and secrete insulin properly,” Hebrok said.
“It has been a major bottleneck for the field.”
“We’re finally able to move forward on a number of different fronts that were previously closed to us,” Hebrok added. “The possibilities seem endless.”
Regardless of starting cell type, the companies say they are ready to churn out their cells in large numbers. Semma, for example, can make more islet cells in a month than can be isolated from donors in a year in the United States, Sanna says, and the company’s “pristine” cells should perform better than donor islets, which are battered by the aggressive techniques required for their isolation.
As these products, some of which have already entered clinical trials, move toward commercialization, regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency have expressed concern about the plasticity of the reprogrammed cells. All three firms subject their cells to rigorous safety testing to ensure that they don’t turn tumorigenic. Before successful trials, companies won’t know the dose of beta cells required for a functional cure, or how long such “cures” will last before needing to be boosted. There’ll be commercial challenges, too: while the companies are investing heavily to develop suitable industrial processes, all acknowledge that no organization has yet manufactured cell therapies in commercial volumes.
Nevertheless, there’s growing confidence throughout the field that these problems will be solved, and soon. “We have the islet cells now,” says Alice Tomei, a biomedical engineer at the University of Miami who directs DRI’s Islet Immuno-engineering Laboratory.
“These stem cell companies are working hard to try to get FDA clearance on the cells.”
Protecting stem cell therapies from the immune system
Whatever the type of cell being used, another major challenge is delivering cells to the patient in a package that guards against immune attack while keeping cells fully functional. Companies are pursuing two main strategies:
- Microencapsulation, where cells are immobilized individually or as small clusters, in tiny blobs of a biocompatible gel.
- Macroencapsulation, in which greater numbers of cells are put into a much larger, implantable device.
ViaCyte, which recently partnered with Johnson & Johnson, launched its first clinical trial in 2014. The trial involved a micro-encapsulation approach that packaged up the company’s partially differentiated, ESC-derived cells into a flat device called the PEC-Encapsulation. About the size of a Band-Aid, the device is implanted under the skin, where the body forms blood vessels around it. “It has a semipermeable membrane that allows the free flow of oxygen, nutrients, and glucose,” says ViaCyte’s chief executive officer, Paul Laikind. “And even proteins like insulin and glucagon can move back and forth across that membrane, but cells cannot.”
The trial showed that the device was safe, well-tolerated, and protected from the adaptive immune system—and that some cells differentiated into working islet cells. But most cells didn’t engraft effectively because a “foreign body response,” a variant of wound healing, clogged the PEC-Encap’s membrane and prevented vascularization. ViaCyte stopped the trial and partnered with W. L. Gore & Associates, the maker of Gore-Tex, to engineer a new membrane. “With this new membrane,” says Laikind, “we’re not eliminating that foreign body response, but we’re overcoming it in such a way that allows vascularization to take place.” The company expects to resume the trial in the second half of this year, provided it receives the green light from the FDA.
Semma is also developing macro¬-encapsulation methods, including a very thin device that in prototype form is about the size of a silver dollar coin. The device is “deceptively simple, but it allows us to put [in] a fully curative dose of islets,” Sanna says.
Semma is also investigating microencapsulation alternatives. At the same time, the company is advancing toward clinical trials using established transplantation techniques to administer donated cadaver cells to high-risk patients who find it particularly difficult to control their blood glucose levels. These cells are infused via the portal vein into the liver, and patients take immunosuppressive drugs to prevent rejection.
Sigilon is working on its microencapsulation technology. Launched in 2016 on the back of work by the labs of Robert Langer and Daniel Anderson at MIT, the company has created 1.5-millimeter gel-based spheres that can hold between 5,000 and 30,000 cells (Nat Med, 22:306–11, 2016). Each sphere is like a balloon, with the outside chemically modified to provide immune-protection, says Sigilon chief executive officer Rogerio Vivaldi. “The inside of the balloon is full of a gel that creates almost a kind of a matrix net where the cells reside.”
In 2018, shortly after partnering with Eli Lilly, Sigilon and collaborators published research showing that islet cells that were encapsulated in gel spheres and transplanted into macaques remained functional for four months. The company has not disclosed a time frame for a type 1 diabetes trial “but we’re moving pretty quickly,” says chief scientific officer David Moller.
Conclusion
To conclude, all three firms hope to extend their work to treat some of the 400 million people worldwide with type 2 diabetes, many of them eventually benefit from insulin injections. The recent endorsements from big Pharmaceutical underline the real progress in beta-cell transplants, says Aaron Kowalski, a molecular geneticist and chief executive officer at JDRF, a foundation based in New York that has funded research at ViaCyte and academic labs whose work has been tapped by Semma and Sigilon. “These companies all realize that if they don’t do it, somebody else will. It’s hard to predict exactly when, but somebody is going to make this work.”
- Published in Blog
Bats Carry Corona Virus. So Why Don’t They Get Sick?
A lot of viruses that has taken a toll on life, the ebola virus in Africa, The Nipah virus of Nipah and the most recent one corona virus that left china running helter skelter all seemed to have originated from bats. During the course of the virus epidemic in Wuhan where it was first detected, some Chinese researchers in Wuhan examined some patients affected in that area and then took samples of the virus.
They did findings on the genetic sequence of the virus with other viruses that were known. The corona virus surprisingly had a 96% match with the horseshoe bats that are dominant in the southwest of china. The research findings were then published in a study on February, 2020.
A virologist Vineet Menachery from the university of Texas Medical Branch at Galveston though not affiliated to the study said “They’re too close in terms of their pure genetics to say they’re not related, or that they didn’t have a common ancestor.”
Menachery was a reputable virologist and had done other research works. He contributed to the theory that the spread of the corona virus must have been from these bats to humans. And possibly must have had another animal that served as an intermediary for the spread.
This same thing had happened with other forms of corona viruses as noted in the case of SARS (Severe Acute Respiratory Syndrome) an outbreak that took place in 2002-2003 where civets, a mongoose family member were infected with the bat corona virus and spread as humans bought them for food.
Another case was the MERS (Middle East Respiratory Syndrome) outbreak. This one happened in 2012 and was as a result of infected camels from the virus. People who ate undercooked meat of camels and as well drank the raw milk of camels were all affected.
So why is it that there are so many diseases that are spread from bats?
Its no doubt, bats have a lot of viruses that they carry with them. And these viruses in their variety are spread and manifests its tolls on people. Scientist are not sure why this is the case as confirmed by Kevin Olival, a research vice president as EcoHealth Alliance, a non-profit organization based in the U.S. He went further to say that it may have something to do with the family of the viruses carried by the bats. So you know, there are over 130 different families of viruses that bats do carry around.
And then, most bats and humans do come in contact through several means. The millions of populations of bats are ubiquitous to all the continents apart from in antartica. Rebekah of Colorado State university who researched infectious pathogens said “There’s a lot of viruses we’re finding in bats because there’s a lot of bats out there.”
They move about in multitudes and live in colonies of large populations. Some these members live in caves and share caves and trees where there can be a contact between humans and bats. Hence, these viruses can spread from these bats to humans.
Despite their sizes, bats have relatively long lifespans and can live over 30 years.”So there’s a long time for them to be persistently infected with the virus and shed it into the environment,” Kading says. The mode of mechanisms for these viruses are through urine, saliva and feces of bats. The outbreak of Nivah that happened in Bangladesh was linked to the sap of a date palm gotten from some trees that some bats licked and had infested with their urine.
Reading through all these, it is not absurd to wonder why the bats themselves do not get affected by the viruses they carry.
The answer to that question is based on the fact that the bat is the only flying mammal in the world. Their body metabolism and process quite differ from that of normal mammals too. When bats fly, their heart rates rise to about a thousand beats per minute with a temperature rise of about 100 degrees Fahrenheit. Linfa Wang a student of bat viruses at Duke-NUS Medical School in Singapore says that when these signs manifest in other mammals, they are signals that can trigger death. But this is not the same case for other bats. This is a lifestyle for them, every day.
Their system is also capable of producing molecules that other organisms do not have. The molecules carry out repair functions and prevent cell damage. This makes their system a bit irresistible to infections and also make them recalcitrant to viruses and resilient to diseases such as diabetes, cancer and other health conditions.
This is a prove that the manifestation of viruses in mammals is not always as a result of the virus itself, but as a result of the body’s reaction to the presence of such a virus that makes us ill by triggering other chain reactions, as Wang explains.
Olival at EcoHealth explains that these bats have coevolved with these viruses and it is not totally their fault that we humans are infected and affected by these viruses. The actual problem is when the viruses move from their species to other species of mammals which is also fostered by human activity.
Naturally, it would be hard for most animals and mammals to cross paths. But Olivial says that the presence of some activities and availability of exchange platforms made available by humans can allow such interaction to occur. She gave an example using wildlife markets like the one in Wuhan, where a bat could be mixed up with a civet. Who later on come in contact with humans – eg. Butchers who do not observe proper hygiene and protection from animal blood.
“The way that we’re coming into contact with these animals, hunting, selling, and trading them is to a scale that really we haven’t seen before,” he says.
Investigative teams did some in-depth search and they discovered some traces of this virus in 22 stalls and in a garbage truck that was found at Huanan Seafood Market right there in Wuhan, a place known for booming trade for live animals. This discovery led to shutting down the market as it was tied to majority of the cases.
The intermediary animals to this viruses are still a mystery, but it is clear that some of these animals are prone to interact more with humans. This is why when they are infected, the likelihood for human infection is widened. These other infected animals can sneeze, urinate, be cooked as food or even owned as pets.
Bats are not just vectors for viruses, they play an important role in balancing the eco-system. They feed on insects and fruits and are active agents of pollination. In fact, Wang believes that since these bats have successfully coevolved with these viruses, there is every possibility that they can be the agents that can lead to the cure and provision of therapies for these viruses.
- Published in Blog
A New Medical Device, in the Management of Complex Wounds
Because of the complex nature of wound healing process, an injury on the skin can pose several challenges and are likely pose complications especially when they are acute. They can as well deteriorate from acute to chronic conditions which will require external intervention best understood by a specialist physician to get the area affected by the wound under normalcy.
The complexity of wound healing and research remains an ocean of knowledge that is continuously researched intensely to uncover depths of wound healing techniques and interventions. Hence, this report contains an introduction and details to the use of a new medical innovation called Gcells used primarily for the management of wounds in their different etiology.
In a case where the process of wound healing seemed difficult, Gcells proved great effects an attribute to their design and working protocol. Gcells are conditioned to work with an enriched suspension of progenitor cells that can efficiently aid tissue repair process. In this case report, two subjects were used as donors and acceptors of these micro-grafts.
Introduction
The skin is an outer layer of the body, offering protection to the underlying layers. A wound breaks this layer and inhibits the various functions as well as expose or also break the underlying layer of tissues. Repair processes are inherent and part of homeostatic processes of the body to try to restore the skin back to its normalcy in structure and in function.
The basics for the skins repair mechanism is represented by a cloth and an inflammation where vessels dilate and monocytes activate leading to breakdown of necrotic tissues. This basic process can be inhibited or delayed by a number of varying factors that lead to deteriorative transformation of acute wounds to chronic forms. But if there is no alteration in the repair process, Mesenchymal cells kickstart proliferative process and begin to repair and restructure the affected tissues starting from the base. At the same time epithelial tissues begin to grow around the wound leading to a final step of the healing process. In this final stage, remodeling of the skin structure is primary and then maturation of a scar.
These processes are efficient best in certain conditions which if affected by factors such as cardiovascular ailment, diabetes, bacterial or any other genre of infection, can inhibit these processes.
Hence, it is necessary to understand in details these processes if there is going to be development or innovation for effective healing processes. Just as stated above, during the proliferative phase of wound healing, Mesenchymal cells are the key role players. Their structure includes a Mesenchymal stem cell (MSCs), multi potent in nature and offer supportive, therapeutic and trophic functions. They are also able to release viable trophic, anti-inflammatory cytokines and anti-apoptotic molecules that offer protection during the repair of wounded skin. MSCs also possess subpopulations that are stem-like nature commonly referred to as “side population” (SP) they have been found out to be enriched in over 1000-fold of progenitor cells and multipotent stem cells and as well exist in tissues and tumors. SP exists in a variety of organs and tissues, after an original discovery to be prominent in the bone marrow of a mouse. The organs with SP include the lung, liver, brain, mammary gland and in skeletal muscles.
In other discoveries, it was discovered that they probably may also be isolated in other tissues of the body. This discovery was in an in vitro and in vivo experiment when Dental Pulp Stem Cells (DPSCs) showed capability to differentiate into osteoblasts and built a woven bone by forming an Extracellular Matrix (ECM) secreted by the osteoblasts. The experiment drew results on the both the quality and quantity of the matrix formed by the DPSCs in the in vivo and in vitro experiment using Stem cells and accompanying biomaterials.
Thus proved that dental pulp holds potentialities of therapeutic strength and a rich source of progenitor/autologous cells that can be used to aid healing processes even applicable to regeneration of craniofacial bones.
This is the evidence that supports the working principle of Gcells innovation. Gcell successfully separates this side population with a size of 50 micron. At this cell population, they can form autologous micro-grafts and can either be used alone or alongside biomaterials prepared in a biocomplex ready for use when necessary.
In this case report, two subjects were used as donors and acceptors of these micro-grafts for enhanced healing of complex wounds through autologous micro-grafts using the Gcell.
Clinical case 1
The first case involves a woman at age 50 who does not have any diseases or disorders. She underwent a laparoscopic gastric bypass surgery and was doing well considering parameters of weightloss. Two years later she moved in for abdominoplasty bariatric. Later on, post complications showed preeminence of necrosis which was discovered after first medical examination were about 150 to 200cm2 at the end of the flaps. An initial necrosectomy showed an intense loss of tissue and we furthered to place the wound on VAC therapy and the patient in active participation of this therapy for one week then at home as an outpatient.
As an outpatient, there was improved and progressive wound cleansing while granulated tissues around the base area were cleared.
The VAC therapy after 2 months still left the margins of the wound deteriorated and surrounding areas not in axis with skin surface.
The Gcell protocol kickstarted after consent from the outpatient. We started by collecting a 3 cm2 skin sample from the patient for the purpose of obtaining the cell suspension needed to be injected to the granulation tissue (figure2).
We followed up with conventional wound treatment as in cleaning and replacement with sterile gauze dabbed with Vaseline. The wound area began to improve in both healing progress and general appearance. In two months, the undermined area disappeared as well as leveled to the axis of the skin surface. 2 months later, the wound reduced to a very little scar that is mild and smoothed compared to the initial condition. (figure 3).
A man who suffered liver cirrhosis, hiatal hernia and diabetic as well at the age of 78. Complex surgery was carried out and distal esophagectomy was performed. But hiatal hernia was not decreased into the abdomen, so he was booked up for corrective surgery. During the intervention the adhesions correlated to the previous abdominal operation and led to opening the colon for resection. Some postoperative complications by the appearance of entero-cutaneous fistulas, related to a colonic anastomosis dehiscence. A second intervention was inevitable hence a ileostomy protection and repackaging of colonic anastomosis. We closed the laparotomy using a biological prosthesis. But we met further complications from ascetic failure that needed intensive care hepatology.
Patient’s condition that included poor liver synthesis had its toll on the healing of the surgical wound. Just as the first case, necrotic tissues grew around the biological prosthesis. We conducted necrosectomy and the biological prosthesis was left half exposed. (Figure 5).
Further treatment of the wound using advanced medication helped cover the biological prosthesis with granulation tissue (figure 6).
Plastic surgeons conducted evaluations on the patient and the choice to do a rotation flap did not seem so appropriate. VAC therapy was used on the wound for about 15 days even though the device wasn’t efficient enough to maintain supposed suction in the presence of ileostomy. We proceeded to treat the patient further with Gcell protocol when wound dimension progressed to about 250cm2. The tissue granulation was of right margin near the ileostomy improved even though it appeared to be undermined. In summary, Gcell protocol has proved a great level of efficiency in healing and restoration of damaged tissues. This progress is certain to open way for employment in the clinical practice that involves the treatment and management of acute and chronic wounds and in any other field of medicine that will inevitably need an instrument to repair lesion on tissues.
Discussion and conclusion
We made it clear earlier in this document about the efficiency of Gcell protocol in its aid to wound healing especially for wounds that are likely to develop from acute to chronic conditions. The working principle for the Gcell used to obtain the viable progenitor cells used for the micrografts relies on one individual as both the donor and the acceptor. This will help to reduce complications that are related to implants or injected micrografts that are non-autologous. Gcell is flexible and can be used both during in operating rooms as well as in ambulatories. This innovation is vastly spreading and currently used in the fields of oral-maxillo-facial field proven by recent studies even though a greater area of its application widespread and acceptable in plastic surgery, dermatology and orthopedics.
Conclusion of this report brings to clarity in demonstration, an efficient, useful and low-risk innovation in the field of medicine, useful for areas in wound management and healing. However, the viability of the Gcell product still needs to be texted on subjects with different conditions and perspectives. But we assure that this device will prove to be a better therapeutic approach in the field of medicine in improving healing of complex wounds. This confidence lies in the excellent features and working principles of this device in obtaining cell suspension, flexibility, facility for procedure and more importantly, the cost. This will help reduce the use of exorbitantly prices devices for advanced medication. In summary, apart from introducing an efficient innovation in the medicine. Gcell has the potentialities to offer employment on clinical procedures that will help aid in the management of wounds no matter how the case may be.
- Published in Blog
Knee replacement alternatives
One of the amputating surgeries in the field of medicine is a knee replacement. It involves removing the knee joint and replacing it with a modified prosthesis. However, several modifications of this surgery have been introduced into the high-powered world of surgery, including several alternatives for knee replacement. In this article, we are going to review the several modifications and knee replacement alternatives therein.
What is Knee Replacement?
Knee replacement, also known as knee arthroplasty, is a surgical procedure that involves the amputation or cutting out of a knee joint, the bones reams by a doctor, especially due to accidents or joint ailments such as arthritis. When the bone is removed, it is then replaced with a prosthetic device. Knee replacement can be partial, where selected or affected parts of the joints can be removed, such as the medial, lateral, and anterior compartments can also be removed and replaced with a modified prosthetic.
Why Should You Be looking for a Knee Replacement Alternatives?
Due to the dynamics of the human body, what works for the goose may not necessarily work for the gander. Certain post-symptoms of a knee replacement can be unbearable for most patients.
Pain After Knee Replacement.
Due to pain in the knee joint, a lot of patients embark on this old-time surgery to help reduce the pain they feel around their knee. But it is worthy of knowing that a substantial number of these patients still continue to feel pain after this audacious surgery. In a survey done by the government, 40% of patients that underwent knee replacement experienced miniature pain for over 3-4 years, while another 44% still felt some 3-5/10 degree of pain in 3-4 years. So, it is not worthy of looking in the direction of knee replacement alternatives in order to solve knee pain.
Knee Replacement Risks.
There is a risk in everything that we do, business, taking a walk, climbing a hill. Same way, certain risks exist in knee replacement which are:
- Patients become more susceptible to heart attack and stroke immediately after knee replacement surgery.
- Increased levels of metals in the blood.
- Allergic reactions to the prosthetic material.
- Possibility of infection.
- Reduced activity of the patient as they thrive to become accustomed to the new prosthesis.
Even though social media and digital marketers paint a vivid picture of beautiful seniors riding a bike, continuing in their daily activities and hobbies, but this may not be true for everyone; in a study conducted by the government, there was seldom activity by patients after knee replacement surgery. Another study showed that patients who weren’t running before a knee replacement surgery couldn’t run after the surgery. But there are always two ways to everything; some other patients also showed an increase in physical activity after their surgery.
What are Knee Replacement Alternatives?
Steroid Injections
Steroids are made up of corticosteroids and cortisone. These corticosteroids carry out an anti-inflammatory function to prevent swelling around the knee regions as well as help reduce pain. But they do have a side effect; they destroy cartilage and may not be efficient as they are thought to be. If you are considering this knee replacement alternative, you probably should bear in mind that they do not offer long term remedies. Steroid injections are viable for knee replacement needs caused by arthritis but may proffer short-termed solutions.
Viscosupplementation
Viscosupplementation is also another knee replacement alternative. They are in the form of gels for the knee, also knowns as hyaluronic acid varying across different brands in the market, likes of SynVisc, OrthoVisc, Supartz, and Euflexxa. They are administered to the patient, but a quick question one would ask is if really the shots help. The variations of results all over the web show support both sides of the notion. But one peculiarity of these results is that none says that they are hurtful or damaging as the steroid injections rather that they give a better solution to knee joint arthritis patients. In my own experience, these injections are efficient only when administered a few times, after which they begin to diminish in effects. The first dose may offer relief for some time, but a dose a far-reaching as the sixth dose may not offer any remedial effect at all.
Knee Nerve Ablation
Knee Nerve ablation is another breakthrough in the surgical world. Knee Nerve Ablation involves the use of technology to carry out a process where the specialist probes the nerves around the joint and passes electrical energy that is used to ablate (destroy) them. The work of these nerves is to relay signals from that region of the knee to the brain. So this technique deadens these nerves, and as such, you don’t feel any pain till those nerves grow back. The research on this type of knee replacement alternative is only a handful. Hence, they cannot conclude on the long term results since most of the studies on this new breakthrough are in their early stages.
Orthobiologics
Orthobiologics incorporation around the knee regions helps to enhance the healing of the knew joint or reduce the consequent degradation of orthopedic tissues. Orthobiologics are also knee replacement alternatives and can be gotten from the patient as autologous or a donor as allogeneic. The two primary derivations of orthobiologics are the PRP and the BMC short for Bone Marrow Concentrate. Another derivation that is commonly used is derived from natal tissues as in amniotic or umbilical cord. Just as the nerve ablation, the research on this type of knee replacement is at its early stages.
Platelet Rich Plasma (PRP)
We mentioned PRP earlier while discussing orthobiologics. PRP’s stand for Platelet-rich plasma that can be gotten from the patient. They contain healing factors that allow them to foster cartilage repair as well as reduce inflammation and balance the chemical dynamics of the knee. A lot of studies support the efficiency of PRP as knee replacement alternatives but may not offer much help when the arthritis is severe.
PKA (Percutaneous Knee Arthroplasty)
PKA (Percutaneous Knee Arthroplasty) comes in handy for severe cases of arthritic pain. This procedure involves the injection of rich bone marrow concentrates gotten from the patient or from a donor into the lax ligaments or other affected areas such as damaged meniscus tissues and tendons. This procedure is intricate and uses an ultrasound and fluoroscopy guides as compared to other quick knee shot techniques. Research proves that this method works pretty well, even in extreme cases of knee arthritis. This procedure also produces a lasting effect for about 2-7 years before the need for repetition.
Here you go!! Knee replacement alternatives. You sure would want to consider some of the alternatives; likes of PKA, PRP, and Bone Marrow concentrates that proffers a long-lasting solution.
- Published in Blog
Conventional and novel stem cell based therapies for androgenic alopecia
Dodanim Talavera-Adame,1 Daniella Newman,2 Nathan Newman1
1American Advanced Medical Corp. (Private Practice), Beverly Hills, CA,
2Western University of Health Sciences, Pomona, CA, USA
Abstract
The prevalence of androgenic alopecia (AGA) increases with age and it affects both men and women. Patients diagnosed with AGA may experience decreased quality of life, depression, and feel self-conscious. There are a variety of therapeutic options ranging from prescription drugs to non-prescription medications. Currently, AGA involves an annual global market revenue of US$4 billion and a growth rate of 1.8%, indicating a growing consumer market. Although natural and synthetic ingredients can promote hair growth and, therefore, be useful to treat AGA, some of them have important adverse effects and unknown mechanisms of action that limit their use and benefits. Biologic factors that include signaling from stem cells, dermal papilla cells, and platelet-rich plasma are some of the current therapeutic agents being studied for hair restoration with milder side effects. However, most of the mechanisms exerted by these factors in hair restoration are still being researched. In this review, we analyze the therapeutic agents that have been used for AGA and emphasize the potential of new therapies based on advances in stem cell technologies and regenerative medicine.
Introduction
The prevalence of androgenic alopecia (AGA) increases with age, and is estimated to affect about 80% of Caucasian men.1 Female AGA, also known as female pattern hair loss, affects 32% of women in the ninth decade of life.2 The consumer market for products that promote hair growth has been increasing dramatically.3 These products promote hair regeneration based on the knowledge about the hair follicle (HF) cycle.4,5 However, in most cases, the mechanisms of action of these products are not well characterized and the results are variable or with undesirable side effects.6 At present, only two treatments for AGA have been approved by the US Food and Drug Administration (FDA): Minoxidil and Finasteride.7–10Although these medications have proved to be effective in some cases, their use is limited by their side effects.11,12 With the emergence of stem cells (SCs), many mechanisms that lead to tissue regeneration have been discovered.13 Hair regeneration has become one of the targets for SC technologies to restore the hair in AGA.14 Several SC factors such as peptides exert essential signals to promote hair regrowth.15,16 Some of these signals stimulate differentiation of SCs to keratinocytes which are important for HF growth.17 Other signals can stimulate dermal papilla cells (DPCs) that promote SC proliferation in the HF.18,19 In this review, we describe HF characteristics and discuss different therapies used currently for AGA and possible novel agents for hair regeneration. These therapies include FDA-approved medications, non-prescription physical or chemical agents, natural ingredients, small molecules, biologic factors, and signals derived from SCs.
HF and SC niche
The HF undergoes biologic changes from an actively growing stage (anagen) to a quiescent stage (telogen) with an intermediate remodeling stage (catagen).4 HFSCs are located in the bulge region of the follicle and they interact with mesenchymal SCs (MSCs) located in the dermal papilla (DP).18 These signal exchanges promote activation of some cellular pathways that are essential for DPC growth, function, and survival, such as the activation of Wnt signaling pathway.19–21 Other signals, such as those from endothelial cells (ECs) located at the DP, are also essential for HF maintenance.22 EC dysfunction that impairs adequate blood supply may limits or inhibits hair growth.22 For instance, Minoxidil, a synthetic agent, is able to promote hair growth by increasing blood flow and the production of prostaglandin E2 (PGE2).7 It has been shown that proteins that belong to the transforming growth factor (TGF) superfamily, such as bone morphogenetic proteins (BMPs), also exert signals to maintain the capacity of DPCs to induce HF growing in vivo and in vitro.23 These BMPs may be released by several cells that compose the follicle, including ECs.24–26 ECs may provide signals for BMP receptor activation in DPCs similar to those signals that promote survival of MSCs in human embryoid bodies composed of multipotent cells.24,25 DPCs have been derived from pluripotent SCs in an attempt to study their potential for hair regeneration in vitro and in vivo.27 Together, dermal blood vessels and DPCs orchestrate a suitable microenvironment for the growth and survival of HFSCs.28,29 Interestingly, the expression of Forkhead box C1 regulates the quiescence of HFSCs located in the bulge region (Figure 1).30 HFSCs are quiescent during mid-anagen and maintain this stage until the next hair cycle.29,30 However, during early anagen stage, these cells undergo a short proliferative phase in which they self-renew and produce new hair.30 Therefore, the bulge region constitutes a SC niche that makes multiple signals toward quiescence or proliferation stages.30–34 It is known that fibroblasts and adipocyte signals are able to inhibit the proliferation of HFSCs.34 Additionally, BMP6 and fibroblast growth factor 18 (FGF18) from bulge cells exert inhibitory effects on HFSC proliferation.34 Dihydrotestosterone (DHT) also inhibits HF growth.35 Agents that reduce DHT, such as Finasteride, promote hair regrowth by inhibiting Type II 5a-reductase.8,14,36 In contrast to these inhibitory effects, DPCs located at the base of the HF provide activation signals (Figure 1).18,34 The crosstalk between DPCs and HFSCs leads to inhibition of inhibitory effects with the resultant cell proliferation toward hair regeneration (anagen).30,31,37 With the self-renewal of HFSCs, the outer root sheath (ORS) forms, and signals from DPCs to the bulge cells diminish in a way that the bulge cells start again with their quiescent stage.4,34As mentioned earlier, Forkhead box C1 transcription factor has an important role in maintaining the threshold for HFSC activation.30 The knockdown of these factors in bulge cells reduces the cells’ threshold for proliferation, and the anagen cycle starts more frequently due to promotion of HFSC proliferation in shorter periods of time.30
Laser therapy
Light amplification by stimulated emission of radiation (LASER) generates electromagnetic radiation which is uniform in polarization, phase, and wavelength.45 Low-level laser therapy (LLLT), also called “cold laser” therapy, since it utilizes lower power densities than those needed to produce heating of tissue. Transdermal LLLT has been used for therapeutic purposes via photobiomodulation.46,47 Several clinical conditions, such as rheumatoid arthritis, mucositis, pain, and other inflammatory diseases, have been treated with these laser devices.48–50 LLLT promotes cell proliferation by stimulating cellular production of adenosine triphosphate and creating a shift in overall cell redox potential toward greater intracellular oxidation.51 The redox state of the cell regulates activation of signaling pathways that ultimately promotes high transcription factor activity and gene expression of factors associated with the cell cycle.52 Physical agents such as lasers have been also used to prevent hair loss in a wavelength range in the red and near infrared (600–1,070 nm).5,47,51,53 Laser therapy emits light that penetrates the scalp and promotes hair growth by increasing the blood flow.54 This increase gives rise to EC proliferation and migration due to upregulation of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase.55,56 In addition, the laser energy itself stimulates metabolism in catagen or telogen follicles, resulting in the production of anagen hair.53,54A specific effect of LLLT has been demonstrated to promote proliferation of HFSCs, forcing the hair to start the anagen phase.57
Biologic agents that promote hair growth and their mechanisms of action
SC signaling
Recently, it has been found that SCs release factors that can promote hair growth.16 These factors and their mechanisms of action have been summarized in Table 3. These factors, known as “secretomes”, are able to promote skin regeneration, wound healing, and immunologic modulation, among other effects.58,59 Some of these factors, such as epidermal growth factor (EGF), basic fibroblast growth factor, hepatocyte growth factor (HGF) and HGF activator, VEGF, insulin-like growth factor (IGF), TGF-ß, and platelet-derived growth factor (PDGF), are able to provide signals that promote hair growth.15,60–64 As mentioned before, DPCs provide signals to HFSCs located in the bulge that proliferate and migrate either to the DP or to the epidermis to repopulate the basal layer (Figure 1).32,65 Enhancement in growth factor expression (except for EGF) has been reported when the adipose SCs are cultured in hypoxic conditions.15 Also, SCs increase their self-renewal capacity under these conditions.66–68 Low oxygen concentrations (1%–5%) increase the level of expression of SC factors that include VEGF, basic fibroblast growth factor, IGF binding protein 1 (IGFBP-1), IGF binding protein 2 (IGFBP-2), macrophage colony-stimulating factor (M-CSF), M-CSF receptor (M-CSFR), and PDGF receptor ß (PDGFR-ß).15,69,70 While these groups of factors promote HF growth in intact skin, another group of factors, such as M-CSF, M-CSFR, and interleukin-6, are involved in wound-induced hair neogenesis.71 HGF and HGF activator stimulate DPCs to promote proliferation of epithelial follicular cells.61 Epidermal growth factor promotes cellular migration via the activation of Wnt/ß-catenin signaling.60 VEGF promotes hair growth and increases the follicle size mainly by perifollicular angiogenesis.72 Blocking VEGF activity by neutralizing antibodies reduced the size and growth of the HF.72 PDGF and its receptor (PDGFR-a) are essential for follicular development by promoting upregulation of genes involved in HF differentiation and regulating the anagen phase in HFs.64,73 They are also expressed in neonatal skin cells that surround the HF.73 Monoclonal antibodies to PDGFR-a (APA5) produced failure in hair germ induction, supporting that PDGFR-a and its ligand have an essential role in hair differentiation and development.73 IGF-1 promotes proliferation, survival, and migration of HF cells.69,74 In addition, IGF binding proteins (IGFBPs) also promote hair growth and hair cell survival by regulating IGF-1 effects and its interaction with extracellular matrix proteins in the HF.70 Higher levels of IGF-1 and IGFBPs in beard DPCs suggest that IGF-1 levels are associated with androgens.74 Furthermore, DPCs from non-balding scalps showed significantly higher levels of IGF-1 and IGFBP-6, in contrast to DPCs from balding scalps.74
Table 3
Stem cell factors and small molecules that promote hair growth and their mechanisms of action
| Factor | Mechanism of action |
|---|---|
| HGF and HGF activator61 | Factor secreted by DPC that promotes proliferation of epithelial follicular cells |
| EGF60 | Promotes growth and migration of follicle ORS cells by activation of Wnt/ß-catenin signaling |
| bFGF62 | Promotes the development of hair follicle |
| IL-693 | Involved in WIHN through STAT3 activation |
| VEGF72 | Promotes perifollicular angiogenesis |
| TGF-ß63 | Stimulates the signaling pathways that regulate hair cycle |
| IGF-169 | Promotes proliferation, survival, and migration of hair follicle cells |
| IGFBP-1 to -670 | Regulates IGF-1 effects and its interaction with extracellular matrix proteins at the hair follicle level |
| BMP23 | Maintains DPC phenotype which is crucial for stimulation of hair follicle stem cell |
| BMPR1a23 | Maintains the proper identity of DPCs that is essential for specific DPC function |
| M-CSF71 | Involved in wound-induced hair regrowth |
| M-CSFR71 | Involved in wound-induced hair regrowth |
| PDGF and PDGFR-ß/-a64 | Upregulates the genes involved in hair follicle differentiation. Induction and regulation of anagen phase. PDGF and its receptors are essential for follicular development |
| Wnt3a97 | Involved in hair follicle development through ß-catenin signaling |
| PGE279,80 | Stimulates anagen phase in hair follicles |
| PGF2a and analogs79,80 | Promotes transition from telogen to anagen phase of the hair cycle |
| BIO98 | GSK-3 inhibitor |
| PGE2 or inhibition of PGD2 or PGD2 receptor D2/GPR4477 | Promotes follicle regeneration |
| Iron and l-lysine95 | Under investigation |
Abbreviations: bFGF, basic fibroblast growth factor; BIO, (2’Z,3’E)-6-bromoindirubin-3′-oxime; BMP, bone morphogenetic protein; DPCs, dermal papilla cells; EGF, epidermal growth factor; GSK-3, glycogen synthase kinase-3; HGF, hepatocyte growth factor; IGF-1, insulin-like growth factor 1; IGFBP-1, insulin-like growth factor-binding protein 1; IL-6, interleukin-6; M-CSF, microphage colony-stimulating factor; M-CSFR, microphage colony-stimulating factor receptor; ORS, outer root sheath; PDGF, platelet-derived growth factor; PDGFR-a, platelet-derived growth factor receptor alpha; PDGFR-ß, platelet-derived growth factor receptor beta; PGD2, prostaglandin D2; PGE2, prostaglandin E2; TGF-ß1, transforming growth factor ß1; VEGF, vascular endothelial growth factor; WIHN, wound-induced hair neogenesis; Wnt3a, wingless-type MMTV integration site family, member 3A.
Small molecules
Small molecules with low molecular weight (<900 Da) and the size of 10-9 m are organic compounds that are able to regulate some biologic processes.75 Some small molecules have been tested for their role in hair growth.76 Synthetic, non-peptidyl small molecules that act as agonists of the hedgehog pathway have the ability to promote follicular cycling in adult mouse skin.76 PGE2 and prostaglandin D2 (PGD2) have also been associated with the hair cycle (Table 3).77 PGD2 is elevated in the scalp of balding men and inhibits hair lengthening via GPR44 receptor.78 Also, it is known that PGE2 and PGF2a promote hair growth, while PGD2 inhibits this process.77,79 Prostaglandin analogs of PGF2a have been used originally to decrease ocular pressure in glaucoma with parallel effects in the growth of eyelashes, which suggests a specific effect in HF activation.80 PGD2 receptors are located in the upper and lower ORS region and in the DP, suggesting that these prostaglandins play an important role in hair cycle.81 Molecules such as quercetin are able to inhibit PGD2 and, in this way, promote hair growth.82–84 Antagonists of PGD2 receptor (formally named chemoattractant receptor-homologous expressed in Th2 cells) such as setipiprant have been used to treat allergic diseases such as asthma, but they also have beneficial effects in AGA.85–87 Another small molecule l-ascorbic acid 2-phosphate promotes proliferation of ORS keratinocytes through the secretion of IGF-1 from DPCs via phosphatidylinositol 3-kinase.88 Recently, it has been described that small-molecule inhibitors of Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway promote hair regrowth in humans.89 Janus kinase inhibitors are currently approved by the FDA for the treatment of some specific diseases such as psoriasis and other autoimmune-mediated diseases.90–94 Also, another group of small molecules such as iron and the amino acid l-Lysine are essential for hair growth (Table 3).95
Cellular therapy
The multipotent SCs in the bulge region of the HF receive signals from DPCs in order to proliferate and survive.27,28,65,84,96 It has been shown that Wnt/ß-catenin signaling is essential for the growth and maintenance of DPCs.19,97 These cells can be isolated and cultured in vitro with media supplemented with 10% fetal bovine serum and FGF-2.37,98 However, they lose versican expression that correlates with decrease in follicle-inducing activity in culture.98 Versican is the most abundant component of HF extracellular matrix.99 Inhibition of glycogen synthase kinase-3 by (2’Z,3’E)-6-bromoindirubin-3′-oxime (BIO) promotes hair growth in mouse vibrissa follicles in culture by activation of Wnt signaling.98 Therefore, the increase of Wnt signaling in DPCs apparently is one of the main factors that promote hair growth.19 DPCs have been also generated from human embryonic SCs that induced HF formation after murine transplantation.27
Platelet-rich plasma
Platelets are anucleate cells generated by fragmentation of megakaryocytes in the bone marrow.100 These cells are actively involved in the hemostatic process after releasing biologically active molecules (cytokines).100–102 Because of the platelets’ higher capacity to produce and release these factors, autologous platelet-rich plasma (PRP) has been used to treat chronic wounds.103 Therefore, PRP can be used as autologous therapy for regenerative purposes, for example, chondrogenic differentiation, wound healing, fat grafting, AGA, alopecia areata, facial scars, and dermal volume augmentation.101,104–108 PRP contains human platelets in a small volume that is five to seven times higher than in normal blood and it has been proven to be beneficial to treat AGA.10,105,109–111 The factors released by these platelets after their activation, such as PDGFs (PDGFaa, PDGFbb, PDGFab), TGF-ß1, TGF-ß2, EGF, VEGF, and FGF, promote proliferation of DPCs and, therefore, may be beneficial for AGA treatment.109,112–114 Clinical experiments indicate that patients with AGA treated with autologous PRP show improved hair count and thickness.109
In search of novel therapies
In this paper, we reviewed and discussed the use of therapeutic agents for hair regeneration and the knowledge to promote the development of new therapies for AGA based on the advances in regenerative medicine. The HF is a complex structure that grows when adequate signaling is provided to the HFSCs. These cells are located in the follicle bulge and receive signals from MSCs located in the dermis that are called DPCs. The secretory phenotype of DPCs is determined by local and circulatory signals or hormones. Recent discoveries have demonstrated that SCs in culture are able to activate DPCs and HFSCs and, in this way, promote hair growth. The study of these cellular signals can provide the necessary knowledge for developing more effective therapeutic agents for the treatment of AGA with minimal side effects. Therefore, advancements in the field of regenerative medicine may generate novel therapeutic alternatives. However, further research and clinical studies are needed to evaluate their efficacy.
Disclosure
The authors report no conflicts of interest in this work.
References
|
Blumeyer A, Tosti A, Messenger A, et al; European Dermatology Forum (EDF). Evidence-based (S3) guideline for the treatment of androgenetic alopecia in women and in men. J Dtsch Dermatol Ges. 2011;9(Suppl 6):S1–S57. |
||
|
Ramos PM, Miot HA. Female pattern hair loss : a clinical and pathophysiological review. An Bras Dermatol. 2015;90(4):529–543. |
||
|
Otberg N, Finner AM, Shapiro J. Androgenetic alopecia. Endocrinolo Metab Clin North Am. 2007;36(2):379–398. |
||
|
Plikus MV, Chuong CM. Complex hair cycle domain patterns and regenerative hair waves in living rodents. J Invest Dermatol. 2008;128(5):1071–1080. |
||
|
McElwee KJ, Shapiro JS. Promising therapies for treating and/or preventing androgenic alopecia. Skin Therapy Lett. 2012;17(6):1–4. |
||
|
Perez-Mora N, Velasco C, Bermüdez F. Oral finasteride presents with sexual-unrelated withdrawal in long-term treated androgenic alopecia in men. Skinmed. 2015;13(3):179–183. |
||
|
Gupta AK, Charrette A. Topical minoxidil: systematic review and meta-analysis of its efficacy in androgenetic alopecia. Skinmed. 2015;13(3):185–189. |
||
|
Shapiro J, Kaufman KD. Use of finasteride in the treatment of men with androgenetic alopecia (male pattern hair loss). J Investig Dermatol Symp Proc. 2003;8(1):20–23. |
||
|
Rossi A, Anzalone A, Fortuna MC, et al. Multi-therapies in androgenetic alopecia: review and clinical experiences. Dermatol Ther. 2016;29(6):424–432. |
||
|
Varothai S, Bergfeld WF. Androgenetic alopecia: an evidence-based treatment update. Am J Clin Dermatol. 2014;15(3):217–230. |
||
|
Rossi A, Cantisani C, Melis L, Iorio A, Scali E, Calvieri S. Minoxidil use in dermatology, side effects and recent patents. Recent Pat Inflamm Allergy Drug Discov. 2012;6(2):130–136. |
||
|
Motofei IG, Rowland DL, Georgescu SR, Mircea T, Baleanu BC, Paunica S. Are hand preference and sexual orientation possible predicting factors for finasteride adverse effects in male androgenic alopecia? Exp Dermatol. 2016;25(7):557–558. |
||
|
Reijo Pera RA, Gleeson JG. Stems cells and regeneration: special review issue. Hum Mol Gen. 2008;17(R1):R1–R2. |
||
|
Jain R, De-Eknamkul W. Potential targets in the discovery of new hair growth promoters for androgenic alopecia. Expert Opin Ther Targets. 2014;18(7):787–806. |
||
|
Park BS, Kim WS, Choi JS, et al. Hair growth stimulated by conditioned medium of adipose-derived stem cells is enhanced by hypoxia : evidence of increased growth factor secretion. Biomed Res. 2010;31(1):27–34. |
||
|
Fukuoka H, Suga H. Hair regeneration treatment using adipose-derived stem cell conditioned medium :follow-up with trichograms. Eplasty. 2015;15:65–72. |
||
|
Du Y, Roh DS, Funderburgh ML, et al. Adipose-derived stem cells differentiate to keratocytes in vitro. Mol Vis. 2010;16:2680–2689. |
||
|
Zhang P, Kling RE, Ravuri SK, et al. A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration. J Tissue Eng. 2014;5:2041731414556850. |
||
|
Tsai SY, Sennett R, Rezza A, et al. Wnt/ß-catenin signaling in dermal condensates is required for hair follicle formation. Dev Biol. 2014;385(2):179–188. |
||
|
Choi YS, Zhang Y, Xu M, et al. Distinct functions for Wnt/ß-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis. Cell Stem Cell. 2013;13(6):720–733. |
||
|
Rao TP, Kuhl M. An updated overview on Wnt signaling pathways a prelude for more. Circ Res. 2010;106(12):1798–1806. |
||
|
Yano K, Brown LF, Detmar M. Control of hair growth and follicle size by VEGF-mediated angiogenesis. J Clin Invest. 2001;107(4):409–417. |
||
|
Rendl M, Polak L, Fuchs E. BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties. Genes Dev. 2008;22(4):543–557. |
||
|
Talavera-Adame D, Gupta A, Kurtovic S, Chaiboonma KL, Arumugaswami V, Dafoe DC. Bone morphogenetic protein-2/-4 upregulation promoted by endothelial cells in coculture enhances mouse embryoid body differentiation. Stem Cells Dev. 2013;22(24):3252–3260. |
||
|
Talavera-Adame D, Wu G, He Y, et al. Endothelial Cells in Co-culture Enhance Embryonic Stem Cell Differentiation to Pancreatic Progenitors and Insulin-Producing Cells through BMP Signaling. Stem Cell Rev. 2011;7(3):532–543. |
||
|
Talavera-Adame D, Ng TT, Gupta A, Kurtovic S, Wu GD, Dafoe DC. Characterization of microvascular endothelial cells isolated from the dermis of adult mouse tails. Microvascular Res. 2011;82(2):97–104. |
||
|
Gnedeva K, Vorotelyak E, Cimadamore F, et al. Derivation of hair-inducing cell from human pluripotent stem cells. PLoS One. 2015;10(1):1–14. |
||
|
Lavker RM, Sun T, Oshima H, et al. Hair follicle stem cells. J Investig Dermatol Symp Proc. 2003;8(1):28–38. |
||
|
Bernard B. Advances in understanding hair growth. F1000Res. 2016;5:1–8. |
||
|
Lay K, Kume T, Fuchs E. FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential. Proc Natl Acad Sci U S A. 2016;113(1): E1506–E1515. |
||
|
Leirós GJ, Attorresi AI, Balañá ME. Hair follicle stem cell differentiation is inhibited through cross-talk between Wnt/ß-catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia. Br J Dermatol. 2012;166(5):1035–1042. |
||
|
Chacon-Martinez CA, Klose M, Niemann C, Glauche I, Wickström SA. Hair follicle stem cells= cultures reveal self-organizing plasticity of stem cells and their progeny. EMBO J. 2017;36(2):151–164. |
||
|
Soler AP, Gilliard G, Megosh LC, O’Brien TG. Modulation of murine hair follicle function by alterations in ornithine decarboxylase activity. J Invest Dermatol. 1996;106(5):1108–1113. |
||
|
Hsu YC, Pasolli HA, Fuchs E. Dynamics between stem cells, nich and progeny in the hair follicle. Cell. 2011;144(1):92–105. |
||
|
Kang JI, Kim SC, Kim MK, et al. Effects of dihydrotestosterone on rat dermal papilla cells in vitro. Eur J Pharmacol. 2015;757:74–83. |
||
|
Yamana K, Labrie F, Luu-The V. Human type 3 5a-reductase is expressed in peripheral tissues at higher levels than types 1 and 2 and its activity is potently inhibited by finasteride and dutasteride. Horm Mol Biol Clin Investig. 2010;2(3):293–299. |
||
|
Osada A, Iwabuchi T, Kishimoto J, Hamazaki TS, Okochi H. Long-term culture of mouse vibrissal dermal papilla cells and de novo hair follicle induction. Tissue Eng. 2007;13(5):975–982. |
||
|
Choi GS, Kim JH, Oh SY, et al. Safety and tolerability of the dual 5-alpha reductase inhibitor dutasteride in the treatment of androgenetic alopecia. Ann Dermatol. 2016;28(4):444–450. |
||
|
Carson C 3rd, Rittmaster R. The role of dihydrotestosterone in benign prostatic hyperplasia. Urology. 2003;61(4 Suppl 1):2–7. |
||
|
Kamimura A, Takahashi T. Procyanidin B-2, extracted from apples, promotes hair growth: a laboratory study. Br J Dermatol. 2002;146(1):41–51. |
||
|
Kamimura A, Takahashi T. Procyanidin B-3, isolated from barley and identified as a hair-growth stimulant, has the potential to counteract inhibitory regulation by TGF-beta1. Exp Dermatol. 2002;11(6):532–541. |
||
|
Ulbricht C, Basch E, Bent S, et al. Evidence-based systematic review of saw palmetto by the Natural Standard Research Collaboration. J Soc Integr Oncol. 2006;4(4):170–186. |
||
|
Rondanelli M, Perna S, Peroni G, Guido D. A bibliometric study of scientific literature in Scopus on botanicals for treatment of androgenetic alopecia. J Cosmet Dermatol. 2015;15(2):120–130. |
||
|
Blume-Peytavi U, Kunte C, Krisp A, Garcia Bartels N, Ellwanger U, Hoffmann R. [Comparison of the efficacy and safety of topical minoxidil and topical alfatradiol in the treatment of androgenetic alopecia in women.] J Dtsch Dermatol Ges. 2007;5(5):391–395. German. |
||
|
Farivar S, Malekshahabi T, Shiari R. Biological effects of low level laser therapy. J Lasers Med Sci. 2014;5(2):58–62. |
||
|
Maiman TH. Biomedical lasers evolve toward clinical applications. Hosp Manage. 1966;101(4):39–41. |
||
|
Cung H, Dai T, Sharma SK, et al. The nuts and bolts of low-level laser (light) therapy. Ann Biomed Eng. 2013;40(2):516–533. |
||
|
Bjordal JM, Couppé C, Chow RT, Tunér J, Ljunggren EA. A systematic review of low level laser therapy with location-specific doses for pain from chronic joint disorders. The Aust J Physiother. 2003;49(2):107–116. |
||
|
Brosseau L, Welch V, Wells G, et al. Low level laser therapy (classes I, II and III) in the treatment of rheumatoid arthritis. Cochrane Database Syst Rev. 2005;19(2):CD002049. |
||
|
Cauwels RGEC, Martens LC. Low level laser therapy in oral mucositis: a pilot study. Eur Arch Paediatr Dent. 2011;12(2):118–123. |
||
|
Schindl A, Schindl M, Pernerstorfer-Schön H, Schindl L. Low-intensity laser therapy: a review. J Investig Med. 2000;48(5):312–326. |
||
|
Liu H, Colavitti R, Rovira II, Finkel T. Redox-dependent transcriptional regulation. Cir Res. 2005;97(10):967–974. |
||
|
Gupta AK, Lyons DCA, Abramovits W. Low-level laser/light therapy for androgenetic alopecia. Skinmed. 2014;12(3):145–147. |
||
|
Jimenez JJ, Wikramanayake TC, Bergfeld W, et al. Efficacy and safety of a low-level laser device in the treatment of male and female pattern hair loss: a multicenter, randomized, sham device-controlled, double-blind study. Am J Clin Dermat. 2014;15(2):115–127. |
||
|
Chen CH, Hung HS, Hsu SH. Low-energy laser irradiation increases endothelial cell proliferation, migration, and eNOS gene expression possibly via PI3K signal pathway. Lasers Surg Med. 2008;40(1):46–54. |
||
|
Tuby H, Maltz L, Oron U. Modulations of VEGF and iNOS in the rat heart by low level laser therapy are associated with cardioprotection and enhanced angiogenesis. Lasers Surg Med. 2006;38(7):682–688. |
||
|
Avci P, Gupta GK, Clark J, Wikonkal N, Hamblin MR. Low-level laser (light) therapy (LLLT) for treatment of hair loss. Laser Surg Med. 2015;46(2):144–151. |
||
|
Rodrigues C, de Assis AM, Moura DJ, et al. New therapy of skin repair combining adipose-derived mesenchymal stem cells with sodium carboxymethylcellulose scaffold in a pre-clinical rat model. PloS One. 2014;9(5):e96241. |
||
|
Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Cir Res. 2007;100(9):1249–1260. |
||
|
Zhang H, Nan W, Wang S, et al. Epidermal growth factor promotes proliferation and migration of follicular outer root sheath cells via Wnt/ß-catenin signaling. Cell Physiol Biochem. 2016;39(1):360–370. |
||
|
Lee YR, Yamazaki M, Mitsui S, Tsuboi R, Ogawa H. Hepatocyte growth factor (HGF) activator expressed in hair follicles is involved in in vitro HGF-dependent hair follicle elongation. J Dermatol Sci. 2001;25(2):156–163. |
||
|
du Cros DL. Fibroblast growth factor influences the development and cycling of murine hair follicles. Dev Biol. 1993;156(2):444–453. |
||
|
Niimori D, Kawano R, Felemban A, et al. Tsukushi controls the hair cycle by regulating TGF-ß1 signaling. Dev Biol. 2012;372(1):81–87. |
||
|
Tomita Y, Akiyama M, Shimizu H. PDGF isoforms induce and maintain anagen phase of murine hair follicles. J Dermatol Sci. 2006;43(2):105–115. |
||
|
Ohyama M, Terunuma A, Tock CL, et al. Characterization and isolation of stem cell – enriched human hair follicle bulge cells. J Clin Invest. 2006;116(1):249–260. |
||
|
Grayson WL, Zhao F, Bunnell B, Ma T. Hypoxia enhances proliferation and tissue formation of human mesenchymal stem cells. Biochem Biophys Res Commun. 2007;358(3):948–953. |
||
|
Potier E, Ferreira E, Andriamanalijaona R, et al. Hypoxia affects mesenchymal stromal cell osteogenic differentiation and angiogenic factor expression. Bone. 2007;40(4):1078–1087. |
||
|
Ren H, Cao Y, Zhao Q, et al. Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions. Biochem Biophys Res Commun. 2006;347(1):12–21. |
||
|
Su HY, Hickford JG, Bickerstaffe R, Palmer BR. Insulin-like growth factor 1 and hair growth. Dermatol Online J. 1999;5(2):1. |
||
|
Batch JA, Mercuri FA, Werther GA. Identification and localization of insulin-like growth factor-binding protein (IGFBP) messenger RNAs in human hair follicle dermal papilla. J Invest Dermatol. 1996;106(3):471–475. |
||
|
Osaka N, Takahashi T, Murakami S, et al. ASK1-dependent recruitment and activation of macrophages induce hair growth in skin wounds. J Cell Biol. 2007;176(7):903–909. |
||
|
Yano K, Brown LF, Detmar M. Control of hair growth and follicle size by VEGF-mediated angiogenesis. J Clin Invest. 2001;107(4):409–417. |
||
|
Takakura N, Yoshida H, Kunisada T, Nishikawa S, Nishikawa SI. Involvement of platelet-derived growth factor receptor-a in hair canal formation. J Invest Dermatol. 1996;107(5):770–777. |
||
|
Panchaprateep R, Asawanonda P. Insulin-like growth factor-1: roles in androgenetic alopecia. Exp Dermatol. 2014;23(3):216–218. |
||
|
Castoreno AB, Eggert US. Small molecule probes of cellular pathways and networks. ACS Chem Biol. 2011;6(1):86–94. |
||
|
Paladini RD, Saleh J, Qian C, Xu GX, Rubin LL. Modulation of hair growth with small molecule agonists of the hedgehog signaling pathway. J Iinvest Dermatol. 2005;125(4):638–646. |
||
|
Nieves A, Garza LA. Does prostaglandin D2 hold the cure to male pattern baldness? Exp Dematol. 2014;(29):224–227. |
||
|
Nelson AM, Loy DE, Lawson JA, Katseff AS, Fitzgerald GA, Garza LA. Prostaglandin D2 inhibits wound-induced hair follicle neogenesis through the receptor Gpr44. J Invest Dermatol. 2013;133(4):881–889. |
||
|
Sasaki S, Hozumi Y, Kondo S. Influence of prostaglandin F2alpha and its analogues on hair regrowth and follicular melanogenesis in a murine model. Exp Dermatol. 2005;14(5):323–328. |
||
|
Choi YM, Diehl J, Levins PC. Promising alternative clinical uses of prostaglandin F2a analogs: beyond the eyelashes. J Am Acad Dermatol. 2015;72(4):712–716. |
||
|
Colombe L, Michelet JF, Bernard BA. Prostanoid receptors in anagen human hair follicles. Exp Dermatol. 2008;17(1):63–72. |
||
|
Zhang Q, Major MB, Takanashi S, et al. Small-molecule synergist of the Wnt/beta-catenin signaling pathway. Proc Natl Acad Sci U S A. 2007;104(18):7444–7448. |
||
|
Fong P, Tong HH, Ng KH, Lao CK, Chong CI, Chao CM. In silicoprediction of prostaglandin D2 synthase inhibitors from herbal constituents for the treatment of hair loss. J Ethnopharmacol. 2015;175:470–480. |
||
|
Weng Z, Zhang B, Asadi S, et al. Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans. PloS One. 2012;7(3):e33805. |
||
|
Norman P. Update on the status of DP2 receptor antagonists; from proof of concept through clinical failures to promising new drugs. Expert Opin Investig Drugs. 2014;23(1):55–66. |
||
|
Pettipher R. The roles of the prostaglandin D(2) receptors DP(1) and CRTH2 in promoting allergic responses. Br J Pharmacol. 2008;153(Suppl 1):S191–S199. |
||
|
Garza LA, Liu Y, Yang Z, et al. Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med. 2012;4(126):126ra34. |
||
|
Kwack MH, Shin SH, Kim SR, et al. I-Ascorbic acid 2-phosphate promotes elongation of hair shafts via the secretion of insulin-like growth factor-1 from dermal papilla cells through phosphatidylinositol 3-kinase. Br J Dermatol. 2009;160(6):1157–1162. |
||
|
Harel S, Higgins CA, Cerise JE, et al. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth. Sci Adv. 2015;1(9):e1500973. |
||
|
Quintás-cardama A, Vaddi K, Liu P, et al. INCB018424 : therapeutic implications for the treatment of myeloproliferative neoplasms Preclinical characterization of the selective JAK1 / 2 inhibitor INCB018424 : therapeutic implications for the treatment of myeloproliferative neoplasms. Blood. 2014;115(15):3109–3117. |
||
|
Geyer HL, Mesa RA. Therapy for myeloproliferative neoplasms: when, which agent, and how? Hematology Am Soc Hematol Educ Program. 2014;2014(1):277–286. |
||
|
Ghoreschi K, Jesson MI, Li X, et al. Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J Immunol. 2012;186(7):4234–4243. |
||
|
Kontzias A, Laurence A, Gadina M, O’Shea JJ. Kinase inhibitors in the treatment of immune-mediated disease. F1000 Med Rep. 2012;4:5. |
||
|
Bao L, Zhang H, Chan LS. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. JAKSTAT. 2013;2(3):1–8. |
||
|
Rushton DH. Nutritional factors and hair loss. Clin Exp Dermatol. 2002;27(5):396–404. |
||
|
Oshima H, Rochat A, Kedzia C, Kobayashi K, Barrandon Y. Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell. 2001;104(2):233–245. |
||
|
Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W. beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell. 2001;105(4):533–545. |
||
|
Yamauchi K, Kurosaka A. Inhibition of glycogen synthase kinase-3 enhances the expression of alkaline phosphatase and insulin-like growth factor-1 in human primary dermal papilla cell culture and maintains mouse hair bulbs in organ culture. Arch Dermatol Res. 2009;301(5):357–365. |
||
|
Sotoodehnejadnematalahi F, Burke B. Structure, function and regulation of versican: the most abundant type of proteoglycan in the extracellular matrix. Acta Med Iran. 2013;51(11):740–750. |
||
|
Xu XR, Zhang D, Oswald BE, et al. Platelets are versatile cells: new discoveries in hemostasis, thrombosis, immune responses, tumor metastasis and beyond. Crit Rev Clin Lab Sci. 2016;53(6):409–430. |
||
|
Lacci KM, Dardik A. Platelet-rich plasma: support for its use in wound healing. Yale J Biol Med. 2010;83(1):1–9. |
||
|
Mussano F, Genova T, Munaron L, Petrillo S, Erovigni F, Carossa S. Cytokine, chemokine, and growth factor profile of platelet-rich plasma. Platelets. 2016;27(5):467–471. |
||
|
Martinez-Zapata MJ, Martí-Carvajal AJ, Solà I, et al. Autologous platelet-rich plasma for treating chronic wounds. Cochrane Database Syst Rev. 2016;(5):CD006899. |
||
|
Modarressi A. Platlet Rich Plasma (PRP) improves fat grafting outcomes. World J Plast Surg. 2013;2(1):6–13. |
||
|
Gentile P, Garcovich S, Bielli A, Scioli MG, Orlandi A, Cervelli V. The Effect of platelet-rich plasma in hair regrowth: a randomized placebo-controlled trial. Stem Cells Transl Med. 2015;4(11):1317–1323. |
||
|
Lynch MD, Bashir S. Applications of platelet-rich plasma in dermatology: a critical appraisal of the literature. J Dermatolog Treat. 2016;27(3):285–289. |
||
|
Trink A, Sorbellini E, Bezzola P, et al. A randomized, double-blind, placebo- and active-controlled, half-head study to evaluate the effects of platelet-rich plasma on alopecia areata. Br J Dermatol. 2013;169(3):690–694. |
||
|
Oh Y, Kim BJ, Kim MN. Depressed facial scars successfully treated with autologous platelet-rich plasma and light-emitting diode phototherapy at 830 nm. Ann Dermatol. 2014;26(3):417–418. |
||
|
Singhal P, Agarwal S, Dhot PS, Sayal SK. Efficacy of platelet-rich plasma in treatment of androgenic alopecia. Asian J Transfus Sci. 2015;9(2):159–162. |
||
|
Valente Duarte de Sousa IC, Tosti A. New investigational drugs for androgenetic alopecia. Expert Opin Investig Drugs. 2013;22(5):573–589. |
||
|
Alves R, Grimalt R. Randomized placebo-controlled, double-blind, half-head study to assess the efficacy of platelet-rich plasma on the treatment of androgenetic alopecia. Dermatol Surg. 2016;42(4):491–497. |
||
|
Cho JW, Kim SA, Lee KS. Platelet-rich plasma induces increased expression of G1 cell cycle regulators, type I collagen, and matrix metalloproteinase-1 in human skin fibroblasts. Int J Mol Med. 2012;29(1):32–36. |
||
|
Mehta V. Platelet-rich plasma: a review of the science and possible clinical applications. Orthopedics. 2010;33(2):111. |
||
|
Leo MS, Kumar AS, Kirit R, Konathan R, Sivamani RK. Systematic review of the use of platelet-rich plasma in aesthetic dermatology. J Cosmet Dermatol. 2015;14(4):315–323. |
- Published in Blog
