The FDA and the Nebraska Department of Health and Human Services recently issued health warnings (also here) after several Nebraska patients became seriously ill following treatment with unapproved cell-based therapies containing exosomes derived from C-section placentas. Because an investigation is ongoing, state health officials could not share further details, including the name of the product used, the source of the placentas, the clinics where the treatments were administered, or the bacteria causing the infections, which included sepsis, although they did say “fewer than five” patients became ill.
According to the FDA, although there are currently no FDA-approved exosome products, clinics in the U.S., including some that market illegal stem cell products, are now also offering exosome treatments to patients. These clinics deceive patients with unproven claims about the potential for exosome products to prevent, treat, or cure various diseases and conditions. Some also claim that that exosome products do not fall under the law governing drugs and biological products, which the FDA says is “simply untrue”. Exosomes used to treat human diseases and conditions are subject to same premarket review and approval requirements as other drugs and biologics.
The clinics currently offering these products outside of FDA’s review process are taking advantage of patients and flouting federal statutes and FDA regulations. This ultimately puts at risk the very patients that these clinics claim to want to help, by either delaying treatment with legitimate and scientifically sound treatment options, or worse, posing harm to patients, as evidenced by these recent reports of adverse events.
What are exosomes?
Exosomes are best defined as extracellular vesicles that are released from cells upon fusion of an intermediate endocytic compartment, the multivesicular body (MVB), with the plasma membrane. This liberates intraluminal vesicles (ILVs) into the extracellular milieu and the vesicles thereby released are what we know as exosomes.
Or, as Paul Knoepfler, Ph.D., Professor at the UC Davis School of Medicine, Department of Cell Biology and Human Anatomy, who helms the excellent Knoepfler Stem Cell Blog, more colorfully puts it for the less scientifically literate (like me):
Imagine if you could bubble up a pea-sized sphere off your skin full of good stuff without harming yourself and toss it over to your relative or friend like a mini-water balloon toss, whose skin would fuse with it and absorb the goodies in side, then becoming healthier.
Sounds like sci-fi at that imagined human scale, but cells do this kind of thing quite often. The cellular ‘water balloons’ are exosomes, tiny subcellular packages containing unique mixtures of various molecules including anything from RNA to proteins.
While Dr. Knoepfler agrees that there is a “growing amount of work and excitement in this area” he says “it’s not entirely clear that this cellular water balloon toss is always beneficial to other cells.” He notes that while stem cell clinics looking for new ways to profit have latched onto the legitimate buzz around exosome research, he “personally doubt[s] the effectiveness of unproven stem cell exosomes as a therapy for many conditions” and warns
there will be risks. Sometimes exosomes from one cell that end up as part of another cell, may negatively influence the health of the other cell. Multiply that by billions or trillions and you can envision possible tissue damage in a hypothetical scenario of things gone wrong.
According to MedPage Today, until 2007, scientists thought exosomes were just a way for cells to get rid of “trash”. However, Swedish researchers showed that some cells use exosomes to transfer genetic material, but what is in them, and their true function, remains a subject of debate.
Like Dr. Knoepfler, Sean Morrison, Ph.D., a stem cell biologist and director of the Children’s Medical Research Institute at the University of Texas Southwestern, is critical of clinics pushing exosomes. He told MedPage Today that “a lot more evidence is required to understand what they are, and it may be that a lot of claims about what they do in the end go by the wayside.” According to Dr. Morrison, the disagreement over whether exosomes have a physiologic function or if they are simply “just some cellular waste product” continues. He added that even the methods for purifying exosomes grown from culture are controversial among scientists “raising questions about what’s in the vials being used in treatment”.
‘What these snake oil salesmen do is they pick a word out of the scientific literature that gets people excited, and they start to sell it,’ Morrison told MedPage Today.
‘The same companies that are willing to ignore FDA requirements for safety and efficacy testing are the same ones willing to ignore regulations for good manufacturing practices and cut corners to sell things that are contaminated with bacteria’, he added.
The Nebraska Department of Health and Human Services warned health care providers and patients that, according to the FDA and CDC, potential risks of unproven stem cell treatments, including placental and umbilical cord blood derived products containing exosomes, include:
- Failure of the cells to work as expected
- Injection site reaction
- Growth of tumors
- Potential for contamination of the product
- The ability of cells to move from placement sites and multiply or change into inappropriate cell types
These potential risks are present even if a patient’s own stem cells are being used.
Other medical and ethical issues are raised by the sourcing of exosomes from C-section placentas. An investigative report revealed that mothers facing C-sections, some in emergency situations, are being solicited to donate their placentas based on the understanding that they will be used to create therapies to help other patients. They are not told that some of these placentas are ultimately sold to the stem-cell industry for use in their dubious treatments.
The growing exosome market
As noted by Dr. Knoepfler, “exosomes are gaining more traction in the unproven stem cell clinic sphere, perhaps in part because of the actions against adipose stem cell clinics.” Google easily turned up clinics all over the country shilling exosomes for unproven uses, often in concert with a variety of questionable treatments, like ozone therapy and vitamin infusions, in addition to other dubious stem cell therapies. Some imply benefits while avoiding making direct claims of effectiveness, although their intent is obviously to make a sale, or at least to make patients inquire. (Otherwise, why would they mention the putative benefits?) Some also use disclaimers, saying that they are not giving medical advice or advising patients that treatments are not FDA-approved.
The regenerative effect of exosomes has been reported in many tissues in the body, such as nerve, heart, liver, kidney, skeleton, cartilage, muscle, pancreas, and dental pulp. Unlike stem cells, they are able to travel systemically without a clumping effect as seen with large doses of stem cell injections, and are small enough to cross the blood-brain barrier. By utilizing exosomes, the cells in our bodies are able to revitalize and produce profound benefits throughout the body.
California: Optimal Health and Wellness [Run by two naturopaths.]
Exosome treatment is a more specialized and heightened version of stem cell enhancing therapy. While stem cells can be used to promote healing as they adapt to surrounding cells, exosomes carry specific signals to instruct cells what to do. . . During exosome treatment, exosomes deliver specific instructions to cells. Signals are directly delivered to cells to for optimal intercellular communication.
[Vastly overstating current scientific knowledge of exosome functioning.]
Delaware: Delaware Integrative Medicine
Exosomes may help regulate processes within the body. Patients with chronic inflammation, autoimmune disease, Lyme disease and other chronic degenerative diseases may benefit from including exosome therapy in their treatment regimen. Exosomes may also be beneficial as part of our Anti-Aging Therapy. Patients with degenerative joint disease have also experienced relief from the use of exosomes.
Missouri: Schoenwalder Health and Wellness
These [exosomes] produce an anti-inflammatory response due to the communication from the many proteins that downregulate inflammatory proteins. Other proteins will then recruit stem cells to the area that will help upregulate these cells to proliferate and promote organized healing through the regulated process. Then, once the task is complete, there are additional proteins that tell the cells when the healing has been completed.
[Again, vastly overstating what is known about the functioning of exosomes.]
Exosomes . . . have been recently reported to play a major role in cell-free therapy of many diseases, including myocardial infarction, drug addiction, and status epilepticus. Our . . . exosome treatments are also thought to help ameliorate inflammation-induced preterm brain injury, liver injury, and various types of cancer.
Georgia: Regenerative Cell Therapy of Georgia
Exosome therapy may be used for the following: Musculoskeletal disorders such as back pain, knee pain, hip pain, cartilage, ligament, tendon damage, nerve injury, degenerated joints, joint pain issues and dysfunction, knee injuries, rotator cuff injury, meniscus damage, muscle tears.
Kansas: The Epigenetics Healing Center [Run by a chiropractor and an MD.]
Anybody with a degenerative or autoimmune condition could potentially benefit from the infusion of certain types of exosome therapies. At this time, it is believed that exosomes could benefit patients with conditions such as: Parkinson’s, Inflammation, Autoimmune diseases, MS. Alzheimer’s, brain injuries, cancer, Lyme disease, diabetes, obesity, and more.
Florida: MD Beauty Labs Spa and Wellness Center [Run by a nurse practitioner. Although Florida law requires nurse practitioners to be supervised by a physician per a written protocol, I could find no reference on the website as to who the supervising physician is.]
Exosomes treatment can be used to treat a range of health concerns. However, it is especially beneficial for those who are living with rheumatoid arthritis or other chronic joint pain.
[Some quotes were reformatted for easier reading.]
Except as noted, all of these clinics are run by MDs or DOs. While aggressive promotion of dubious treatments is par for the course for chiropractors and naturopaths, there is something deeply disturbing about the violation of ethical and professional norms evident when physicians offer treatments that they know perfectly well are unproven, potentially dangerous and, according to the FDA, illegal. Physicians who become aware of such conduct should remember their duty to report it to appropriate authorities, such as peer review bodies and state licensing boards. That duty is set forth in the AMA’s Code of Medical Ethics Opinion 9.4.2, “Reporting Incompetent or Unethical Behavior by Colleagues”.
The obligation to report incompetent or unethical conduct that may put patients at risk is recognized in both the ethical standards of the profession and in law and physicians should be able to report such conduct without fear or loss of favor.
Of course, neither the reporting party nor the treatment provider need be a physician to report “sketchy” stem cell clinics and there are a number of options for anyone to take action by alerting the appropriate state and federal authorities.
- Check to make sure the product being considered is on the FDA’s approved list of stem cell treatments .
- If the stem cell product is not on the approved list, ask the provider to show you that they have FDA permission to research a new drug, which requires what’s called an Investigational New Drug (IND) Application number and acknowledgement communication issued by the FDA.
- Request the facts and ask questions if you don’t understand. To participate in a clinical trial that requires an IND application, you must sign a consent form that explains the experimental procedure. The consent form also identifies the Institutional Review Board (IRB) that assures the protection of the rights and welfare of human subjects. Make sure you understand the entire process and known risks before you sign. You also can ask the study sponsor for the clinical investigator’s brochure, which includes a short description of the product and information about its safety and effectiveness.
- Ask for this information before getting treatment – even if the stem cells are your own.
The FDA is also asking health care professionals and consumers to report any adverse events related to exosome products (or any other unapproved product) to the FDA’s MedWatch Adverse Event Reporting program.