Where do adult stem cells come from?
Adult stem cells receive a lot of interests in the scientific community, thanks to their ability to self-renew and generate numerous types of cells and tissues. Based on their provenience, stem cells are categorized as embryonic stem cells and adult stem cells.
Unlike embryonic stem cells, which have the ability to differentiate into more than one cell type, most adult stem cells types are capable of forming only the types of tissues that they are part of. However, due to the controversy surrounding embryonic stem cell use, more and more researchers turn their attention to the study of adult stem cells.
As a result, we now know of several adult tissues that serve as sources for stem cells. This is great news for people who suffer from degenerative conditions like osteoarthritis, muscular dystrophy and even Alzheimer’s disease.
The list of adult tissues known to contain stem cells is growing and it includes bone marrow, the brain, peripheral blood and blood vessels, skeletal muscle, liver and pancreas.
Adult stem cells can be obtained from multiple tissues
Neural brain cells (NSCs) are multipotent cells which generate the central nervous system. They undergo asymmetric cell division, resulting in one non-specialized (blank) cell and one specialized cell. Japanese researchers have been able to use NSCs to replace dying neurons on mice . Currently there are numerous ongoing investigations on the response of NSCs in multiple sclerosis (MS) patients and Parkinson’s disease patients. The results may have future applications in the treatment of neurological conditions.
Hematopoietic stem cells (HSCs) are stem cells isolated from blood or bone marrow. They can differentiate into variety of specialized cells, such as white blood cells, which fight infection, red blood cells, which carry hydrogen and platelets, which are responsible for blood clotting.
The downside of HSCs is that the ratio of HSCs in bone marrow is 1 in every 10,000-15,000 cells, which slows down the harvesting process considerably. Bone marrow also hosts skeletal stem cells (STCs), which give rise to osteoblasts (bone cells), cartilage and hematopoietic stroma.
An interesting niche of stem cells is the one lining the surface of the small and large intestines (ISCs). This type of stem cells divide continuously throughout life and are believed to be the source of most forms of cancer of the small intestine and colon. The longevity and renewal rates of ISCs becomes problematic in colorectal cancer, because they promote the regeneration of the tumor after therapy.
In healthy adults, the liver is responsible with maintaining the balance between cell gain and cell loss. Its impressive regenerative functions are attributed to hepatocytes, which are believed to be the adult stem cells of the liver. When the liver tears apart from virus infections, inflammation or is sectioned through hepatectomy, hepatocytes activate a stem cell-like behavior, giving rise to new tissue, replacing the lost liver cells.
Another important discovery has been made by Dr. Lola Reid of the University of North Carolina, accredited expert in the research of liver development . As it turns out, the biliary tree, a network of vessels which connect the liver and pancreas to the intestine, generates a special type of adult stem cells. Their major characteristic is being pancreatic precursor cells, meaning they are destined to differentiate as pancreatic cells.
In a series of lab tests, these biliary cells have been manipulated to become islets, structures responsible for the production of insulin and c-peptide, a key component in the natural production of insulin. As a result, the blood sugar control in the subject mice has increased dramatically. Dr. Reid hopes that her team’s efforts will speed up the process of finding a cure for diabetes.
In conclusion, the past few decades of scientific research have provided us with great insight on adult stem cells and their applications in regenerative medicine.
Unlike embryonic stem cells, they can be isolated from a variety of adult tissues– such as the brain, bone marrow, peripheral blood and even tumor-derived tissue cells- allowing scientists to avoid an ethical dilemma entirely. The risk of rejection is considerably lower (the donor is usually the patient himself) and the differentiation rates are higher, giving much hope for the future research of cures for degenerative conditions in humans.
REFERENCES: MacKlis, Jeffrey D.; Magavi, Sanjay S.; Leavitt, Blair R. (2000). “Induction of neurogenesis in the neocortex of adult mice”. Nature 405 (6789): 951–5
 Biliary Tree Stem Cells, Precursors to Pancreatic Committed Progenitors: Evidence for Possible Life-long Pancreatic Organogenesis – http://www.diabetesresearch.org/file/research-publications/2013-Stem-Cells_Biliary-Tree-Stem-Cells-to-Islets.pdf
Autoimmune disorders are conditions in which the sufferer’s body produces substances that attack the healthy cells of the organism, as it doesn’t distinguish between the healthy tissues and antigens. There are more than 80 types of autoimmune conditions known today, among which diabetes type 1, systemic lupus erythematosus, rheumatoid arthritis, celiac disease, myasthenia gravis and multiple sclerosis.
The exact cause of these ailments is unknown, but scientists believe that viruses, bacteria or certain drugs may trigger some internal changes that confuse the organism and cause the immune system to react by destroying the healthy tissues. Besides the damage caused to healthy cells, autoimmune conditions also lead to changes in organ function and may cause the abnormal growth of organs.
These disorders may affect several tissues or organs, but the most common areas that are destroyed by the immune system include the red blood cells, skin, connective tissues, blood vessels, endocrine glands (mostly the pancreas and thyroid), joints and muscles.
Currently, the standard treatment for autoimmune conditions is represented by immune suppressive agents, but these medications only induce temporary improvements, and don’t cure the disorders completely. For this reason, scientists have started to investigate the potential use of stem cells in autoimmune disorders.
In animal studies, stem cell therapy with mesenchymal stem cells has been shown to induce healing activity in various autoimmune disorders, and to prevent the destruction of healthy tissues by the immune system. But what does research say about treating autoimmune disorders in humans? Are stem cells effective in this case as well?
THE USE OF STEM CELLS IN AUTOIMMUNE DISORDERS IN HUMANS
Mesenchymal stromal stem cells have been found to exert immunological functions under inflammatory conditions, a study published by researchers at the Department of Internal Medicine, Erasmus MC, Rotterdam in Arthritis Research and Therapy showing that MSCs play an important role in maintaining immune homeostasis .
According to researchers, MSCs do not have immune cell effector functions and are not “true” immune cells, but can play a role in the initiation of immune responses. Unlike immune T- and B-cells, mesenchymal stem cells do not poses receptors for recognizing the antigens, but they do express pattern recognition receptors, which enable the stem cells to recognize microbes.
In conclusion, the mentioned study showed that although MSCs do not fit the exact definition of immune cells, they do influence the body’s immune response and can act as regulators or coordinators of the immune system .
In another paper published in the Nature journal, scientists at the Massachusetts General Hospital, Harvard Medical School have showed that hematopoietic stem cells may be used in treating severe autoimmune diseases, like rheumatoid arthritis or multiple sclerosis .
The stem cell therapy investigated by the US researchers involved the transplantation of HSC following an immunosuppressive treatment like chemotherapy or radiotherapy. This treatment was found to be effective in curing autoimmune diseases in animal models, and most patients who received allo-HCT achieved remission of the disorder, although there were also exceptions.
Researchers at the Stem Cell Technology Research Center, Tehran have investigated the use of stem cell therapy in multiple sclerosis patients. Their review paper, published in the International Journal of Hematology-Oncology and Stem Cell Research, showed the following: neural stem cells derived from the adult central nervous system may have neuroprotective and immunomodulatory effects, so they may be a solution for treating MS .
Mesenchymal stem cells derived from bone marrow also have a potential for migration into the inflamed tissues of the central nervous system and are able to differentiate into neuronal cells. In mice, MSCs helped in improving the neurological function of animals with experimental autoimmune encephalomyelitis (EAE). The application of stem cells in humans with multiple sclerosis was also investigated by scientists at the American University of Beirut Medical Center, Lebanon, who showed that bone marrow mesenchymal stem cells may lead to clinical improvements in patients with advanced multiple sclerosis .
Another autoimmune condition in which stem cells may be useful is rheumatoid arthritis, studies showing that human amnion mesenchymal cells isolated from the placenta may be feasible for treating collagen-induced arthritis in rats . These cells have immunosuppressive functions and can ameliorate the severity of arthritis, so they may be a promising therapy for RA sufferers.
Despite these positive results, there are still a lot of challenges to overcome when it comes to treating autoimmune disorders with stem cells, so scientists need to establish precise protocols for all these conditions that could be treated through stem cells therapy.
Cartilage and bone deterioration are a common consequence of aging, but poor diet, sedentary lifestyle, excess weight or injury can also result in damaged tissue. Unlike bone tissue, mature cartilage is avascular and doesn’t heal well after injury. Replacement or augmentation surgery is one way to fix a torn joint, but the costs are high and there are also several risks involved in the procedure, such as transplant rejection and infection .
In January 2015, scientists at the Stanford University School of Medicine published a paper regarding their latest findings in tissue engineering. With the use of skeletal stem cells (myoblasts), they have been able to give rise to bone and cartilage in mice. In addition, they mapped out the chemical signals which can create skeletal muscle stem cells, directing their development into specialized types of cells .
To better understand the medical significance of these findings, we are going to take a closer look at stem cells and their role in bone and cartilage regeneration.
HOW SKELETAL STEM CELLS ARE OBTAINED
Stem cells (or blank cells) are undifferentiated cells that can divide or differentiate into specialized cells, replacing dying cells or damaged tissues. There are two broad types of stem cells: embryonic stem cells (ESCs) and adult stem cells (somatic stem cells).
ESCs are harvested from embryos 4-5 days post-fertilization, at each time they consist of 50-150 cells. Embryonic stem cells are pluripotent and can repair damaged tissue or stimulate the regeneration of diseased cells. However, due to ethical controversy, the study of ESCs is a slow process.
In humans, bone marrow, peripheral blood and adipose tissue are rich sources of adult stem cells, but these can be also harvested from some brain areas, skin, liver and even teeth. Until recent years, it was thought that adult stem cells differentiate only as the type of tissue they originate from. Emerging studies suggest that just like ESCs, these cells can specialize in unrelated cell types, as well.
The study conducted at the Stanford University School of Medicine supports these claims. The research focused on groups of cells with a fast division rate, located at the ends of mouse bones. Human skeletal muscle-derived cells were transplanted into host mice.
Prior to the procedure, the targeted host tissues were modulated by irradiation and cryoinjury, to allow the observation of the transplanted cells in mice. After four weeks of observation it was discovered that these isolated collections of cells were able to reconstruct all parts of the mouse bone.
Through further investigation, scientists were able to map the developmental tree of skeletal stem cells, which provided great insight on how to give rise to more specific types of cells. Irving Weissman, MD professor of pathology and of developmental biology, who directs the Stanford Institute for Stem Cell Biology and Regenerative Medicine, hopes that once these findings are translated into humans, the odds of rescuing cartilage and bone from wear and aging will increase significantly .
DIFFERENTIATION OF SKELETAL STEM CELLS AND THERAPEUTIC APPLICATIONS
Skeletal muscle is a dynamic tissue, capable of a regenerative response within a couple of weeks. This ability is primarily due to its satellite cells populations, a type of cells that are located peripheral to the myofiber.
When injury or disruption occurs, these satellite cells become activated and either fuse together to replace the damaged myofiber or multiply at an increased rate, supporting additional rounds of regeneration. In addition, skeletal stem cells can also give rise to blood derivatives, vascular components, osteoblasts (bone formation cells), adipocytes (fat cells) and cartilage .
The use of skeletal stem cells for therapeutic purposes brings hope to patients who suffer from muscular conditions, including muscular dystrophy. Joint pain, dislocations and arthritis are also on the list of potential stem cell therapy. Rheumatoid arthritis, Osteoarthritis and even Multiple Sclerosis patients could also benefit from these findings in the not-too-distant future.
The main challenge of using myoblasts for cell therapy remains, for now, harvesting and culturing them up to the numbers required.
 David King – Development and remodeling of skeletal tissue, School of Medicine, Southern Illinois University, 2009 http://www.siumed.edu/~dking2/ssb/skeleton.htm#development
 Christopher Vaughan – Researchers isolate stem cell that gives rise to bones, cartilage in mice, Stanford Institute for Stem Cell Biology and Regenerative Medicine, 2015 https://med.stanford.edu/news/all-news/2015/01/researchers-isolate-stem-cell-that-gives-rise-to-bones-cartilage.html