Obstacles and Opportunists
A brief look at the current state of stem cell therapy
By: Sienna Schaeffer
The first successful bone marrow transplant was performed in 1956 in Cooperstown, New York by Dr. Edward Donnell “Don” Thomas (1). The patient had a type of blood cancer called leukemia. The bone marrow was donated by the patient’s identical twin. This transplant was a remarkable achievement in the history of medicine and part of the reason why Don Thomas won the 1999 Nobel Prize in Medicine. It was also the first known successful use of stem cell therapy to treat disease. Today an internet search reveals hundreds of clinics offering stem-cell based therapies that purport to treat a wide variety of conditions. Unfortunately many of these clinics may not be offering much treatment at all.
Sixty-two years and thousands of transplants after Don Thomas’s first successful procedure, bone marrow transplants remain one of the very few FDA-approved stem cell-based therapies. Approved therapies include bone marrow transplants for cancer patients and cord blood (blood from the placenta and umbilical cord after birth), which is approved to treat certain blood and immune disorders (2).
Stem cells have the potential to treat a great number of diseases — cardiac disease, neurological disease, joint pain, and more. The promise stems (hehe) from the cells’ unique properties. Most cells in your body have a pretty limited life as far as reproduction goes. Many of them can divide a limited number of times to produce other cells that look exactly like them, while many others do not divide at all. The two key properties that set stem cells apart from other cells are unlimited divisions and the ability to give rise to cells that will develop into specialized cells such as muscle, hair, or skin cells. So each time a stem cell divides, it can produce either another stem cell or a more specialized cell.
Embryonic stem cells are masters of cellular plasticity and each can give rise to the complete array of human cell types. Adult stem cells, on the other hand, have limited repertoires for what their daughter cells can become. There are certain types of adult stem cells and each type produces a set of specialized cells. For example, spermatogonial stem cells can only give rise to sperm cells, whereas hematopoietic stem cells can give rise to all of the cells that make up your blood, including red blood cells and all the different types of white blood cells. Hematopoietic stem cells are the only type of stem cells in use in all of the FDA-approved stem cell therapies.
Scientists recognized the therapeutic potential of stem cells decades ago. However there’s still a long way to go before they are a widely used therapy due to some pretty serious complicating factors. For example, Dr. Thomas’s successful bone marrow transplant was not only preceded but also followed by a slew of failed transplants. In 1970, a review article was published on 203 human bone marrow transplants. Of the 203 patients who received transplants, 152 died before their physicians even wrote their case reports, and most of the rest were dead before the time of the review article (3). The high failure rate was due in part to issues of genetic compatibility between the donors and patients. Many people are familiar with the concept of blood types and the need for compatibility between a blood donor and recipient. The compatibility is necessary because your immune system is designed to distinguish between ‘you’ and ‘not you,’ based on signals present on the outer surface of your cells. Think of them as little notes that say “I’m with you! I’m healthy! Please don’t kill me!” Someone who is genetically compatible with you has signs that look enough like yours to trick your immune system into accepting any transplanted cells. In the early days of bone marrow transplants scientists and physicians were aware that such signals existed, but they didn’t know what they were or how to check for them.
Although there have been vast improvements in our understanding of genetic compatibility, the dangers of adverse immune responses remain a major obstacle to the development of any type of stem cell therapy. Unfortunately it is one of only many serious obstacles. The journey to creating an effective stem cell therapy is a long one. Scientists must typically begin by figuring out how to create the desired cell type from stem cells. This can be an arduous process, given the myriad of functions that each of our cell types is required to perform. Once functional cells have been created, there are still a huge number of questions to be answered: where should they be put? Is there any improvement after a transplant? If there is improvement, are the cells responsible for the improvement? Do the cells cause an immune response? If so, is there a way to prevent it? Do the cells fix the underlying disease state or will they be damaged just like the original cells if there is no additional intervention? When should the stem cells be administered? Is there a point that is too late? Plus, each disease system that is a potential target for stem cell therapy comes with its own unique array of complications and challenges.
There are also some serious safety concerns which must be continually monitored and addressed. Aside from immune rejection, the major concern that hangs over all stem cell treatments is the potential that the patient will develop cancer. This is a risk inherent in the use of stem cells, as cancer is the result of uncontrolled cell growth and stem cells naturally have the ability to divide essentially indefinitely. Researchers are continually making progress answering these questions and developing procedures to make stem cell therapies as safe as possible, but so far there has not been an explosion of stem cell treatments readily available to the public.
This may be surprising to anyone who has ever googled ‘stem cell therapy.’ Such a search reveals a myriad of clinics promising to treat cardiac conditions, degenerative neurological disorders, pulmonary disorders, etc. Some clinics also offer stem cell treatments for cosmetic complaints (4).
What exactly are these clinics offering then, if no stem-cell therapies have been approved to treat these diseases? Drs. Leigh Turner and Paul Knoepfler found that there are 351 companies with 570 clinics across the U.S. offering a variety of stem cell interventions. Most of these companies (~⅘) were advertising ‘autologous cell-based interventions,’ which means that a patient’s own cells would be used for the treatment. The remaining ~⅕ clinics advertised allogeneic interventions, meaning that the tissue given to the patient came from a different human being. The common sources for these allogeneic interventions are amniotic material, placental tissue, and umbilical cords — basically the tissues left over after a baby is born (4).
One clinic system in Minnesota offers treatments for ‘degenerative musculoskeletal, skin, and soft tissue conditions,’ including but not limited to partially torn ligaments and tendons, knee meniscus injury, osteoarthritis, painful erections/intercourse, and erectile dysfunction. The treatment begins with liposuction or bone marrow harvesting to isolate ‘a vast array of regenerative cell populations.’ These cells are injected into the damaged tissues of the patient. Inside the patient, they do something that allegedly causes some kind of improvement.
It should be acknowledged that there are several aspects of this therapeutic approach that are consistent with what we know about stem cells. There stem cells in bone marrow and fatty tissue. They are called mesenchymal stem cells, or MSCs. MSCs can give rise to daughter cells with a variety of fates: bone, fat, muscle, cartilage, tendons, skin, and even some neural cells. Animal models of stem cell treatments using MSCs have shown that they may be useful in a wide variety of therapies, including diabetes, heart disease, lung injury, and more. MSCs can evade host immune responses and they do secrete substances that cause nearby cells to repair themselves. Plus, unlike some other kinds of stem cells, they can actually be given to the patient systematically, say in the form of an IV, because they are thought to be able to respond to and move towards damaged tissues in the body.
This may sound rather tempting to many people suffering from the conditions that this procedure allegedly treats. Truth be told, the idea sounds amazing — who wouldn’t want to trade a little fat from their midsection for pain reduction or elimination in their joints? Unfortunately, there’s more to the story. There is simply no guarantee that this treatment is safe, let alone effective. Although animal models of MSC-based treatments have shown promising results, success in animal models often fails to translate into success in humans. Since no form of this treatment has been approved by the FDA, we don’t know exactly what these clinics are doing. Are they actually isolating MSCs from bone marrow or adipose tissue? What are they doing to make sure those cell populations are safe to put back into the patient — not contaminated by a pathogen or abnormal cells? With no oversight or regulation, patients cannot be sure about what they are getting when they agree to undergo these unapproved treatments.
The FDA has recently indicated that it intends to ‘crack-down’ on clinics offering unapproved stem cell therapies. The crack-down was inspired in part by a patient-funded stem cell therapy clinical trial for a treatment for macular degeneration which went very wrong and left three patients blinded. Subsequent investigations, including a report by Dr. Turner, led to an alarming realization: a number of companies are conducting patient-funded clinical trials for stem cell based treatments.
Patient-funded clinical trials are uncommon because they present serious logistical and ethical complications that could be the subject of their own article. Suffice to say that most of the concerns about patient-funded trials center on unnecessary exposure to patients, financial and emotional exploitation of in dire circumstances, and a lack of scientific rigour before and during the trial. These patient-funded trials often have flaws built in to the very design of the study, rendering any results they produce unreliable (5).
For example, in a number of the studies Dr. Turner found both the physicians and patients are aware of which patients are receiving treatment and which are not. This is highly unusual — the ‘gold standard’ of clinical trials requires that both the providers and patients be unaware who is receiving the actual treatment and who is receiving a placebo. This practice is called ‘double blinding,’ and researchers use it to distinguish between the actual action of the drug and the placebo effect, a term used to describe the physical and/or emotional responses to a treatment often produced by our own minds.
Stem cells are by definition cells full of potential, but in the current world of medicine their uses are somewhat limited. If you have leukemia, lymphoma, aplastic anemia, an immune deficiency disorder, or any other condition treatable by bone marrow transplant, stem cells may be your safe and effective path back to health. For the rest of us, only time will tell if stem cells can live up to their seemingly unlimited promise.
If you or a loved one are considering undergoing unapproved stem cell-based procedures, consider visiting this website for tips on how to make an informed decision about potential treatments.
Bibliography
- Mukherjee, S. (2010). Emperor of All Maladies. Scribner: New York, NY.
- FDA. (2017). FDA Warns About Stem Cell Therapies. https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm286155.htm
- Bortin, M.M. (1970). A compendium of reported human bone marrow transplants. Transplantation 9(6): 571–587.
- Turner, L., Knoepfler, P. (2016). Selling Stem Cells in the USA: Assessing the Direct-to-Consumer Industry. Cell Stem Cell 19(2): 154–157.
- Future Science Group. (2017). Stem Cell Clinics Registering for-profit, pay-to-participate studies on clinicaltrials.gov. https://www.eurekalert.org/pub_releases/2017-07/fsg-scc071917.php
