Title: Journal Club Review – Commercial Stem Cells: The Wild West of Stem Cell Therapeutics
August’s journal club was led by Shannon Walsh (Graduate Student in Corinne Henak’s lab). Journal club review was written by Grant Hisao (Postdoc in Katie Henzler-Wildman’s Lab).
Stem cells are characterized as pluripotent cells, meaning they are unspecialized and capable of gaining specific function. Stem cells can be embryonic (from embryos), autologous (adult stem cells from one’s self), allogeneic (adult stem cells from another human), or xenogeneic (adult stem cells from another species), and, because of their pluripotent nature, stem cells are thought to be a useful tool in regenerative medicine. This has led many people to think stem cell therapies are miracle treatments that could cure anything. However, much like pharmaceuticals and medical devices, the development of stem cell therapies has required years of research and testing for safety.
The United States Food and Drug Administration (FDA), the governmental entity with the jurisdiction to regulate stem cell treatment, has approved only a handful of treatments. Most of these treatments use cells isolated from bone marrow or blood to treat cancer or specific conditions related to one’s blood or immune system. Unfortunately, the lack of oversight and the desire for individuals seeking a panacea for their medical conditions has led to an explosion of fraudulent stem cell clinics around the world. These clinics purport stem cell treatment as a cure for almost anything, employing techniques that are far from medically valid or safe while charging top dollar, and putting desperate patients in medical danger and financial peril. This field of bogus medicine has been referred to as “the wild west of stem cells” and was the topic of discussion at CaSP’s science policy journal club for the month of August.
Rise of Rogue Stem Cell Treatment
Medical tourism is defined as the act of traveling to another country or state to receive medical care that is deemed illegal or unavailable in one’s domiciled location. Many stem cell treatments gained popularity through the medical tourism industry, involving clinics in other countries (e.g. China, India, etc.). In the past decade stem cell clinics have boomed within the United States, with clinics springing up in population centers such as California, Florida, and the Northeast. A study by Leigh Turner and Paul Knoepfler published in 2016 identified 351 businesses marketing some sort of stem cell treatments at 570 clinics.
In many cases, these stem cell clinics advertise on their website’s unproven treatments for a gamut of conditions. In the case study discussed at journal club, three women received stem cell treatment for macular degeneration. The treatment was conducted by a clinic called U.S. Stem Cell (previously called Bioheart) in Florida, where each participant paid $5,000 to have stem cells isolated from their own fat be injected into their eyes (i.e liposuction and magical eye treatment for the price of one). Shortly after treatment, each woman went blind. More recently, the Washington Post and CBS This Morning published a story of a Georgia woman receiving similar treatment (Stem Cell Center of Georgia), which resulted in the same depressing outcome.
Commercial stem cell treatments come with a number of adversities, including both physical and financial harm to patients, weakening the scientific research process, as harming public opinion of science and medicine. The major problem exposed by all of these cases is the lack of regulation. Many stem cell treatments are experimental and are listed on the website clinicaltrials.gov (managed by the National Institutes for Health). What is misleading, however, is that trials listed on the website may not have governmental approval, allowing clinics to deceive patients into thinking that these experimental treatments are legitimate. So, the questions that beg to be answered are 1. how are stem cell treatments regulated? and 2. how are these rogue practices still operating?
Stem Cell Regulation
In 2001, within three years after the first reported the ability to isolate and culture human embryonic stem cells (Jamie Thomson’s group at UW-Madison), the FDA issued part 1271 of the Code of Federal Regulations 21 (21 CFR 1271), which regulates “human cells, tissues, and cellular and tissue-based products (HCT/P’s).” Under 21 CFR 1271, HCT/P’s are subject to regulations governed by section 351 of the Public Health Service Act (PHS). Under 351 PHS, any drug, device, or biologic is subject to series of regulations which requires the item to undergo the Biologic License Application (BLA) process. This time consuming and expensive process makes some companies uneasy, but does allow some product exemptions.
To meet the exemption standards, companies need only to state that their HCT/P is “minimally manipulated,” “intended for homologous use,” and “is for autologous use” (e.g. stem cells from fat can perform the same basic function as cells in the eye). Furthermore, clinics can argue under 1271.15 that their procedure simply “removes HCT/P’s from an individual and implants such HCT/P’s into the same individual during the same surgical procedure,” thus exempting their treatment altogether from regulation. To summarize, companies claim that if a procedure uses a patient’s own cells, their own cells should not be regulated like a pharmaceutical regardless of how legitimate the procedure is. Furthermore, without FDA oversight, these clinics can operate in daylight with little to no repercussion.
Changes In Regulation?
In August 2017, the FDA announced a new effort to enforce regulations on stem cells. In May of this year, the Department of Justice filed two civil injunctions against two different clinics (one in Florida, one in California). While both of these actions hint at the government’s seriousness in cracking down on this growing problem, little else is being done at a policy level to fix this problem. Rather, 2018 brought us the Right to Try Act, which allows terminally ill patients the opportunity to try treatments that have only passed Phase I clinical trials. If anything, the Right to Try Act may enable more individuals to take riskier treatments with unknown consequences.
To gain more insight in the direction of stem cell therapies, our journal club discussion leader, Shannon Walsh, shared some of the opinions provided by Prof. R. Alta Charo, professor of law and bioethics at UW-Madison. While most of us at journal club thought legislation as being the primary solution to the problem, Prof. Charo believes that legislation will not necessarily change the culture. Rather, she believes that it is imperative for professional societies in research and medicine to develop and inform the best practices for stem cell use and to encourage members of these societies to employ these practices. Furthermore, she believes that insurance providers can also help steer the direction by working with the medical/research societies in identifying legitimate treatments that can be covered by insurance and rejecting procedures that are fraudulent. Lastly, it is important to educate patients on the risks and regulations associated with any treatment.
The Future of ‘the Wild West”
With the onslaught of stem cell clinics, limited resources in regulation, and the vibrant “Right to Try” mentality, solutions seem distant. However, I believe it important to take Prof. Charo’s final point of patient education to heart. Aside from understanding the risks involved with any medical treatment, it is vital that we as medical patients understand the regulatory status of any treatment and identify any red flags. Here are a few reminders/red flags to look for when researching experimental treatments:
- Just because a treatment is listed on clinicaltrials.gov doesn’t mean that a treatment is approved by the government.
- Legitimate clinical trials rarely charge for treatment (i.e. if there is a large price tag associated with an experimental treatment, it’s probably a scam).
- If a clinic claims their treatment is FDA approved, verify that information with the FDA (the FDA has approved only a handful stem cell treatments).