Medical applications of exosomes
Exosome therapy is gaining popularity in regenerative medicine. So what exactly are exosomes? Exosomes are particles that are released but cannot be replicated. They are intrical in how cells talk to each other. One cell will have a bunch of vesicles that leave and head to another cell to deliver a “message.” These vesicles contain information in the form of chemicals, cytokines to particles of messenger RNA.
Where are Exosomes found?
Exosomes are produced from stem cells and can be found in a variety of tissues.
How are they different from Stem Cells?
Exosomes are contained in stem cells. They are messenger cells that travel to communicate with other cells to produce the needed proteins to repair damaged areas. The use of exosomes does not require donor cells to be injected in the body. Exosomes can be extracted from mesenchymal stem cells (MSCs), sterilized and then injected into the body.
Stem cell therapy injects donor cells into a specific location. These stem cells grow and divide to repair the injured area and create healthier cells overtime. Exosomes are extracted from mesenchymal stem cells and like stem cells are injected into the injured area. Exosomes get to work at communicating with the patient’s own cells and enhance communication among the cells to generate the necessary and needed cells for healing.
What Exactly is Exosome Therapy ?
Exosome products are generally used for orthopedic injuries. Much like stem cell therapy, the exosomes would be injected into the injured site. This is generally an outpatient therapy that is relatively painless.
What does Exosome Therapy Treat? (Medical applications)
Exosome therapy is used for a variety of musculoskeletal injuries, chronic pain, degenerative diseases and genetic disorders. Aging and injuries suppress your cells ability to communicate with each other. The whole purpose of exosomes is to promote communication between cells to repair damaged tissues.
Exosomes are also used to help repair the skin from effects of aging. Overtime, the dermal layer of the skin is damaged because of fragmentation in the collagen, resulting in the signs of aging and hindering the ability to heal wounds. Exosomes have been found to help the body ramp up its collagen production. Exosomes also help inhibit inflammatory cytokines. This means exosomes can help with Atopic Dermatitis, a common skin disorder.
Exosomes can also help with lyme disease. Lyme disease is a very complex disease that compromises the immune system. This can lead to the disruption of cellular health and function. Oftentimes, lyme disease patients experience difficulty with inflammation which exosomes are also known to treat.
Are Exosomes Safer than Stem Cells
While both therapies have a low risk of complications, exosome therapy does not involve a surgical procedure for harvesting cells. Stem cells’ primary job is to grow and divide new and healthy cells from the donor cells. At times these cells may rapidly multiply resulting in a tumor. Exosomes do not multiply, rather they are responsible for improving the communication among cells.
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What is Exosome Therapy?
Some of the most cutting edge treatments in regenerative medicine today are based on exosome therapy. Studies of this cellular therapy have yielded optimistic prospects, and have shown that exosomes can be used in a wide array of applications and types of treatments.
Being such a new therapy, it is important to know their chief characteristics, how they work, and the functions that they are responsible for, as well as how these details are crucial in treatment with exosomes.
What Are Exosomes?
Exosomes are small extracellular vesicles that are secreted by cells. They are responsible for intercellular communication, where they basically act as messengers carrying valuable protein signals and genetic information (DNA & RNA) between the cells.
They can spread throughout the whole body, delivering messages that tell the cells how to behave, what is happening in the nearby area, or what they should be producing. These messengers are produced by the cells in our own body naturally, and Stem Cells are the chief producers.
What Does Treatment With Exosomes Entail?
Exosomes, being mainly produced by stem cells, have been hypothesized as a treatment for the regeneration of tissue.
This was discovered during investigations in which it was observed that the repairing effect of stem cells can be replicated using only exosomes. This, in turn, opened the door to a method of regenerative medicine therapy that is completely free of stem cells.
The treatment is simple. Immediately upon applying the exosomes directly into a wound or deteriorated tissue, it will improve the communication among affected cells. These exosomes will send proteins which help cells to both regulate themselves and repair tissue.
What Can Exosome Therapy Treat?
As it is capable of regenerating many different types of tissue, exosome therapy is chiefly applied in the treatment of wounds and to diminish the effects of wear and aging on the body. Where treating wounds are concerned, exosome therapy has been proven empirically to produce two effects upon application:
A notable decrease in pain and inflammation: this is the first potential effect. This is due to exosomes being rich in immunomodulatory proteins which both facilitate and regulate the immune response of the human body. This is done through T Cells and NK Cells, which leads to reduced pain and swelling in the affected area.
Repairing and Remodeling of Tissue– the second possible effect is because exosomes have the remarkable ability to instruct other cells around them to repair themselves and surrounding tissue. This brings with it long-lasting regeneration and symptom relief.
How Is This Treatment Applied?
One of the principal application routes is via injection directly into the wounded area– or the area in which one desires treatment. Exosome ampules administered in this form can count on a high concentration of exosomes, along with a smaller concentration of other cellular components like cytokines and chemokines, being delivered into the patient.
This procedure does not require any heavy set-up time, and can be realized in a clinic. Injection can be done with a fine needle to reduce any possibility of pain, and there is no recovery time required after the application.
Who Can Use Exosome Therapy?
This cell-free regenerative medicine treatment can be very beneficial for people suffering from a wide variety of illnesses. Currently, research is being conducted to discover the true reach that this treatment has– but nevertheless, marked improvement has been found in patients suffering from chronic inflammation, immune-system disorders, degenerative diseases and Lyme disease.
The deterioration that the body can suffer as a result of genetics, environmental factors, or caused by chronic diseases can be assuaged upon receiving a high dose of exosomes, which reduce inflammation and spur repairing in the tissues.
Learn More About Treatment With Exosomes
In a matter of years, the number of applications exosomes are being used for has multiplied in several different fields of interest. Currently, it is being studied for its use as a cellular therapy treatment with no cells, as well as in regenerating tissue, diagnostics, and the treatment of cancer, among other promising studies.
Gordie Howe’s Stem Cell Treatments Support a Growing Appeal for These Therapies Among Athletes and Baby Boomers
In October, 2014, legendary hockey player Gordie Howe, then 86, was on death’s door after suffering a debilitating acute hemorrhagic, left thalamus stroke. Upon returning home from the hospital, Howe needed someone to lift him from his bed to a wheelchair and back. He couldn’t remember the names of his four children, Marty, Mark, Cathy, and Murray, and his condition continued to grow worse in subsequent weeks. According to an article in New York Magazine, when Mark took hid father to get an epidural to relieve his back pain, the attending physician took one look at Gordie and asked Mark if it might be better to just let his father go. On the rare occasion when Gordie did mange to speak, he would tell his children, “Just take me out back and shoot me.”
Howe retired from hockey at age 52, having scored more goals than any other player. But over the past 10 years, his health declined dramatically—heart disease, dementia, and spinal stenosis—despite his family’s and physician’s best efforts to find medical solutions. After his stroke, Keith Olbermann aired a preemptive obituary on ESPN. The family made funeral plans. Murray, his youngest son, wrote a eulogy.
Around Thanksgiving, 2015, Howe’s family learned about an experimental stem cell treatment that could save his life. The plan was to inject up to 100 million neural stem cells into his spinal column in the hopes that the stem cells would migrate to his brain and help his body repair itself. Howe could improve within 24 hours, and receive the treatment anytime—just not in the United States. The procedure wasn’t FDA-approved, and Howe would have to receive the treatment at a clinic in Tijuana.
Howe’s son Murray, a radiologist, looked into the treatment and thought it was promising. The real concern was transporting the immobile Howe to Mexico. Daughter Cathy worried that he might die during the treatment, but Mark responded bluntly: “If he does die, what’s the difference? He’s going to be gone soon no matter what.”
While the family weighed the stem cell treatment idea, Howe was admitted to the hospital with severe dehydration, caused by his unwillingness to swallow. When he returned home, he still had no use of his right side, and the family
assumed he would never walk again. The Howe children decided to give the stem cell treatments a try.
Two days later, the Howes flew their Dad to San Diego. In the air, Gordie grew agitated and got the attention of a flight attendant, who spent 10 minutes kneeling by his seat trying to understand something he wanted to tell her. Due to his profound memory loss, Howe didn’t know he had suffered a stroke, why he was on a plane, or where he was going. But he remembered one thing, which he managed to whisper to the fight attendant: “I was a pro hockey player.”
The next morning, Marty and Murray drove with their father across the border to Clínica Santa Clarita, where Gordie bent over a table to expose his lower back so that a needle could be inserted into his spinal canal to inject the stem cells. Howe was given two types of stem cells – neural stem cells and mesenchymal stem cells. The second type, derived from bone marrow, has anti-inflammatory properties and secretes chemicals that promote healing.
The procedure then required Howe to lie prone for eight hours. After the eight hours passed, Gordie told Murray he needed to use the bathroom and that he intended to walk there in order to do so. Since the stroke, Gordie had only managed to walk one time—10 steps, with a walker. Murray reminded his Dad that he couldn’t walk.
Howe stood up, and with Murray’s support, walked for the first time in more than a month—to the bathroom. This milestone became an oft-repeated story among the Howe family, and Gordie’s revival became an irresistible story for the sports pages. Back home, Gordie returned to something resembling the normal life of an 86-year-old. He pushed the grocery cart, helped with the dishes, and could go fishing so long as one of his sons reminded him that a tug on the line meant he needed to start reeling. The family released a video of Gordie standing stationary, firing a puck, five-hole, past his 8-year-old great-grandson. Keith Olbermann apologized for his premature obituary.
Howe’s children now had to figure out how to share his apparent recovery—a debate that proved just as contentious as their decision to fly him to Mexico for the treatment in the first place—with the world. Both Marty and Mark had played in the NHL alongside their father, but now Murray, the doctor, was giving interviews in his hospital scrubs, endorsing his father’s place in medical “miracle” history. He began referring to the stem-cell treatment as the “Gordie Howe Protocol,” and said that his Toledo-based hospital was looking into conducting an FDA-approved study of the procedure. In one interview, Murray Howe stated that “stem cells are the most promising thing in medicine since the discovery of antibiotics.”
As the story spread, the medical community started to question just how miraculous Howe’s recovery had been.
“Companies selling these products are preying on desperate and vulnerable people and exploiting their hope, much like snake-oil salesmen have done throughout most of human history,” wrote Judy Illes and Fabio Rossi, stem-cell experts at the University of British Columbia, in the Vancouver Sun. Even advocates pointed out that, though the field holds great promise, no reputable studies have shown that such a procedure should work.
And yet, for the children of ailing parents, such skepticism doesn’t matter. Murray’s response to one skeptic was, “What would you do for your father?”
Gordie Howe’s therapy, would cost an average patient about $30,000.
Athletes, whether playing or retired, have a special need for the regenerative capacity that stem cells are believed to provide. Athletes break bones, strain ligaments, bash knees and wear out cartilage. If stem cells’ restorative capability is proven, they could be considered the latest form of sports medicine.
Since Howe’s treatment in late 2014, two other athletic legends have received stem cell treatments—former quarterbacks Bart Starr and John Brodie. And the rest of the population, particularly aging baby boomers, isn’t far behind.
Still, while acceptance of stem cell therapy has grown, so have controversies surrounding its use. While clinical trials authorized by the U.S. Food and Drug Administration are rapidly expanding in the U.S., so are treatments outside the regulated system. Patients are going to stem cell clinics in other countries that approve stem cell therapies.
For its part, the FDA is drafting guidelines, although the U.S. and Canada still trail other countries in approving stem cell treatments.
Last year, the FDA issued draft guidelines to clarify what types of human cell therapy it regulates. The short answer: Most of them, with “limited exceptions,” according to an FDA email sent in response to questions from The San Diego Union-Tribune. These exceptions include cells or tissues that are “minimally manipulated,” not given with any other product and perform the same function in the donor as in the recipient.
All other stem cell therapies are seen as involving human cells, tissues and cellular and tissue-based products – also known as HCT/Ps – regulated by the FDA’s Center for Biologics Evaluation and Research.
“We understand that determining the appropriate regulatory path for HCT/Ps can be challenging, and the FDA is working diligently to develop guidance to help sponsors and physicians understand how to apply federal regulations to this complex and emerging field,” the agency said.
In January 2015, University of California, Davis stem cell researcher and blogger Paul Knoepfler estimated that more than 100 unauthorized stem cell clinics were operating in the United States. Later that year, he increased that estimate to up to 200.
Then on May 6, he wrote on his blog: “We are seeing a flood of professional athletes getting stem cell treatments in the past few years.”
Athletes and others who want these treatments bristle at what they call cumbersome, time-consuming regulations in the U.S. The situation can be urgent for seriously ill patients.
While it hasn’t been proven that the stem cells enabled his recovery, by all indications Gordie Howe’s health has improved significantly since receiving stem cell treatments. In November, 2015, Murray Howe said that his father’s physicians in the U.S. recommended hospice care in the weeks after the stroke, and the family was told he wouldn’t last more than two or three weeks,
“Then, suddenly, he is raking and sweeping and goofing around in the back yard,” Murray said.
Sources: The San Diego Union-Tribune, New York Magazine
The British Broadcasting Corporation (BBC) recently reported that stem cell transplant treatments normally used for cancer patients are helping Multiple Sclerosis (MS) patients in the UK. According to the January 18, 2016 report, 20 patients received bone marrow stem cell transplants using their own stem cells, and that at least some of the patients who were paralyzed by MS are able to walk again post-treatment.
Approximately100,000 people in the United Kingdom suffer from MS, with most new patients diagnosed between the ages of 20 and 30 years of age.
“To have a treatment which can potentially reverse disability is really a major achievement,” says Prof Basil Sharrack, of Sheffield’s Royal Hallamshire Hospital in Sheffield, England.
The treatment, known as autologous hematopoietic stem cell transplantation (HSCT), involves the intravenous infusion of autologous or allogeneic stem cells harvested from the patient’s own bone marrow to reestablish hematopoietic function (formation of blood or blood cells) in patients whose bone marrow or immune system is damaged or defective by chemotherapy. Using stem cells harvested from the patient’s bone marrow helps rebuild the immune system. The theory is that these newly harvested cells are at such an early stage in development that the cellular defects that result in MS do not exist.
“The immune system is being reset or rebooted back to a time point before it caused MS,” says Prof John Snowden, consultant hematologist at Royal Hallamshire Hospital.
The BBC’s Panorama program spoke to several MS patients who have undergone the stem cell transplant.
Steven Storey was diagnosed with MS in 2013 and, within a year, went from being an able-bodied athlete to wheelchair dependent and losing sensation in much of his body.
“I went from running marathons to needing 24-hour acute care. At one point I couldn’t even hold a spoon and feed myself,” Storey says.
Within a few days of the transplant Storey was able to move his toes, and after four months he could stand unaided.
While Storey still needs a wheelchair for mobility, he calls his progress astounding.
“It’s been incredible,” he says. “I was in a dire place, but now I can swim and cycle and I am determined to walk.”
The Royal Hallamshire Hospital along with hospitals in the United States, Sweden and Brazil, is part of an international clinical trial called MIST that is assessing the long-term benefits of the stem cell procedure on MS patients. Study participants all have relapsing remitting MS (RRMS), and received intensive chemotherapy to completely destroy the patients’ immune systems.
Treatment costs are about the same as the annual cost for existing treatments, and the stem cell treatment does not require the use of new or existing medications.
Prof Richard Burt of Northwestern University in Chicago carried out the first hematopoietic stem cell transplantation for MS in 1995, and is coordinating this current MIST international trial, which began in 2006.
“There has been resistance to this in the pharma and academic world,” Burt says. “This is not a technology you can patent and we have achieved this without industry backing.”
A study published last year involving MS patients in Chicago showed significant reductions in neurological disability, and for some the improvements persisted for at least four years, although there was no comparative control group.
The outcomes of the current international trial will be reported in 2018, and may determine whether the stem cell transplant becomes a standard in the United Kingdoms health care system for many MS patients.
“Ongoing research suggests stem cell treatments such as HSCT could offer hope, and it’s clear that in the cases highlighted by Panorama they’ve had a life-changing impact,” says Emma Gray, M.D., head of clinical trials at UK’s MS Society.