CHANGES IN HOW “STEM CELL CLINICS” ARE REGULATED BY THE FDA & INFERTILITY

CHANGES IN HOW “STEM CELL CLINICS” ARE REGULATED BY THE FDA - and how that pertains to the infertility field

According to Forbes, 1 the FDA in 2016 warned the public for the first time about so-called for-profit “stem cell clinics” that offered a variety of alleged stem cell therapies with claims of curing everything from COVID-19 and Alzheimer’s disease to hair loss and aging. In an article from November 2022, the NIH tried to “put stem cell-based therapies into context,” 2 noting that the FDA over the past three decades has approved several stem cell-based products, including bone marrow transplants, which have been transformational for many cancer patients, and therapies for blood and immune system disorders. Other approved treatments included products for dental uses and tissue growth and foreskin burns. 

Since the early 2000s, stem cell-based therapies have been explored in many eye diseases, including age-related macular degeneration and glaucoma. 2 Stem cell-based therapies are also being explored for neurodegenerative diseases such as stroke and Alzheimer’s disease, and for countless other conditions. The article then, however, also noted that increasing numbers of rogue clinics had started taking advantage of patients desperate for cures by claiming dramatic results, often exaggerated in sensational media testimonials. Those clinics – according to the authors – often mimic legitimate medical practices that extract a patient’s own stem cells, concentrate or modify the cells, and then re-inject them. Some manufacturers offer stem cell-based derived products, such as “biologic eye drops” made with placenta extract or amniotic fluid to treat dry eye. Those clinics also often provide misleading information and advertise their practice as running clinical trials without, of course, following standard required clinical trial rules, including registration and/or FDA regulatory approval.

The article further noted that these unproven and unregulated stem cell treatments carry significant risk, from administration site reactions to more dangerous systemic adverse events. For example, injected cells can multiply into inappropriate cell types or even dangerous tumors. A 2017 report, indeed, described one Florida clinic that blinded patients with stem cell eye injections. 3 The authors also noted that the Pew Charitable Trusts gathered 360 reports of adverse events related to unapproved stem cell therapies, including 20 cases that caused death. 4 Further, adverse events are likely underreported because these products are not FDA approved or regulated. Many unproven stem cell-based therapies cost thousands of dollars to patients and are not covered by insurance. Further, even if patients avoid adverse events from these therapies, they may suffer consequences from delaying evidence-based treatments.

A legal blog recently addressed this subject 4 based on the fact that the legal authority of the FDA to regulate what was happening in such clinics was unclear and a recent court case established some clarity. The blog described the case as follows: This case required a decision whether the FDA can regulate certain stem cell mixtures advertised as treatments for a host of medical conditions. Defendants were doctors who created such a mixture by removing fat tissue from a patient and breaking it down to concentrate the portion containing (mesenchymal) stem cells. The result was a mixture of stem cells, other types of cells, and cell debris called stromal vascular fraction (SVF), which then was administered for example directly into a patient’s knee to treat osteoarthritis. In recent years, clinics offering similar stem cell mixtures have proliferated despite concerns over whether such treatments are safe and effective.

Without going into further legal detail (for that the reader is referred to reference #4 which in great detail very well explains how the appellate court reached its conclusions in a logical and stepwise approach), the FDA wone the case with the court deciding that what the clinic did was inject a drug/ treatment which gave the FDA the authority to oversee the process.

Practically, this means that the FDA has the authority to regulate “stem cell clinics” and the question that now arises is how interested the FDA will be in shouldering this burden and how aggressively the agency, therefore, will end up pursuing these “rouge” clinics, as classified by the NIH. 2 What all of this means for infertility: For infertility practice, we see two potential consequences: The first relates to the use of stem cells in infertility practice and we currently are aware of two potential applications: the use of bone marrow-derived stem cells in the treatment of Asherman’s syndrome which has entered human applications in formal clinical trials,5,6 and the use of stem cells for intraovarian “rejuvenation” treatments which have been successfully investigated in a mouse model 7 but, to the best of our knowledge, have not yet been investigated in human trials, though we are aware of companies 8 and IVF clinics 9 already advertising such treatments.

The CHR is concerned about the injection of stem cells into ovaries without at least prior proper safety studies in animal models because stem cell therapies for some time have been known to carry a risk of cancer induction, 8 and ovarian tissue is known to be cancer prone. 9 The second relevant issue that arises from above noted court case is a question asked in response to the detailed report on the trial by the blog 4 involving the use of platelet rich plasma (PRP). PRP has, of course become widely utilized worldwide in fertility clinics, both intrauterine as well as intraovarian.

Above-described court decision, however, does, indeed, raise the question whether injection of PRP can be equated to injection of stem cell products? The answer is more likely no than yes, but good arguments can be made on both sides: On the one hand, it seems likely that certain excep- tions published by the FDA may apply. For example, the FDA allows for such an exception if tissues are immediately returned into the body of the patient, which is usually the case with PRP treatments. On the other hand, an argument for FDA supervision can be made, considering how different production of PRP is in different clinics, and how much clinical protocols differ. Likely the most important argument for better control over PRP treatments in infertility is, however, their still questionable utility, considering the scarcity of published trials.

In contrast to most other fertility clinics, the CHR, therefore, considers the use of PRP in infertility still as an experimental procedure and – moreover – is conducting several clinical trials of the use of PRP in different patient groupings.

REFERENCES

1. Haseltine WA. Forbes. November 13, 2021. https://www.forbes. com/sites/williamhaseltine/2021/11/13/unregulated-stem-cell-clinics-endanger-patients-and-limit-research/

2. Wai et al., NIH. November 16, 2022. https://www.nih.gov/about-nih/what-we-do/science-health-public-trust/perspectives/putting-stem-cell-based-therapies-context

3. Kuriyan et al., N Engl J Med 2017;376(11):1047-1053 

4. Segal J. Medical Justice Blog. November 1, 2024. https://medicaljustice.com/blog/regulation-of-stem-cell-clinics-sands-are-shifting/

5. Benor et al., J Assist Reprod Genet 2020;37(7):1511-1529

6. Flores et al., Fertil Steril 2024;122(4Suppl):E36-37)

7. Elias et al., eBioMedicine 2023;94:104715

8. https://ovoskill.com/Meyer-Hermann M. Sci Reports 2018;11776

9. American Cancer Society. https://www.cancer.org/cancer/types/ovarian-cancer/causes-risks-prevention/risk-factors.html