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Unregulated Stem Cell Clinics Proliferate in the US, Despite 2013 Court Ruling

Shaw, Gina

doi: 10.1097/01.NT.0000473456.60330.09
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Three years after the US District Court ruled that stem cell treatments could be defined as drugs and should be regulated, the number of stem cell clinics continues to rise. Stem cell experts call for tighter regulation from the Food and Drug Administration and better patient education.

Three years ago, the US District Court ruled in United States v. Regenerative Sciences, LLC that stem cell therapy fell within the Federal Food, Drug, and Cosmetic Act's definition of a drug, making it subject to federal regulations. As Neurology Today reported in an article in January 2013, stem cell research experts fully expected the ruling to put the brakes on unlicensed clinics offering this unproven therapy for neurologic disorders like Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS).

But more than two years later, a quick Internet search reveals that the opposite has happened. More clinics than ever are extolling the benefits of extracting and culturing mesenchymal stem cells from a patient's own body and creating a mixture that is then injected back into the patient.

“We are able to offer patients access to cutting-edge adipose stem cell therapy for each of the degenerative diseases” using autologous stem cell transplants, claims StemGenex, of La Jolla, CA, listing treatments for Alzheimer's, Parkinson's, and MS. “Groundbreaking advancements in autologous stem cell treatment are giving patients the ability to fight back against diseases once thought untreatable,” declares the Florida-based Stemedix. And Cell Surgical Network, with branches all over the country, says that it is “currently studying” autologous stem cell transplants from adipose tissue to treat neurologic conditions like ALS, MS, Parkinson's, Alzheimer's, and muscular dystrophy.

“I think it has gotten worse because now it's becoming more mainstream,” said Arnold R. Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research in the department of neurology at the University of California, San Francisco. “Many stem cell ‘therapy’ websites make the treatment sound as if it's an acknowledged, proven form of therapy for many types of neurologic diseases, orthopedic problems, and other conditions. In none of these cases has it actually been proven to be effective.”

But not for lack of trying, said Clive Svendsen, PhD, director of the Regenerative Medicine Institute at Cedars-Sinai Medical Center in Los Angeles. “There have been hundreds of placebo-controlled trials with mesenchymal stem cells to try and substantiate some of these claims,” he told Neurology Today. “Results are not dramatic, and they tend to last only a few days — otherwise this would become standard therapy. If something works, it goes very quickly into the clinic.”

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As the relentless advertising of these clinics continues unabated, researchers are calling for more Food and Drug Administration (FDA) oversight. In an editorial in the New England Journal of Medicine (NEJM) in September, Hermes Taylor-Weiner, PhD, and Joshua Graff Zivin, PhD, pointed to a loophole in the FDA's regulations classifying biologic products as either “351 cells” or “361 cells.” The 351 cells have been grown in culture or genetically manipulated; they are subject to strict regulatory oversight and require FDA approval for use. Cells classified as 361 have been “minimally manipulated” for use in the same patient and are for “homologous use,” meaning the tissue must perform similar functions before and after it has been transplanted. It's this classification that stem cell clinics claim, arguing that the primary function of stromal vascular fraction (SVF) cells — the adipose-derived stem cells — is regeneration, both before and after extraction.

“The FDA guidelines do not clarify whether homologous use means the transplanted tissue must perform all its prior functions or only some of them,” noted Drs. Taylor-Weiner and Zivin.

The FDA also allows a product to qualify under 361 if it is removed from a patient and re-implanted during the same surgical procedure.

“This provision was developed so people could use vascular autografts. The instructions were very clear that the cells could not be manipulated in any way,” said Ole Isacson, MD, a professor of neurology at Harvard Medical School, director of the Neuroregeneration Research Institute at McLean Hospital, and a principal investigator at the Harvard Stem Cell Institute. “But these clinics have been skirting the intention of that regulation, preferring to take the risk of being closed down. The FDA doesn't have enough personnel to investigate all these clinics, and patients, in their desperation, are seeking them out.”

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The FDA's inability to regulate the situation raises several risks, argued Dr. Kriegstein. “Primary among them is misleading patients into thinking this is a demonstrated effective therapy,” he said. “Patients are being charged quite a lot of money [anywhere from $5,000 to $50,000], most of which is not covered by insurance. At worst, it impoverishes these patients. At best, it diverts their resources from approaches that are more likely to provide relief.”

There are also safety concerns. “Patients with a whole variety of medical conditions are subjected to systemic administration of these cells, and we don't know exactly how they're going to respond or how their conditions will react, especially patients with immune or autoimmune conditions,” Dr. Kriegstein warned.

“The cells being introduced are autologous, and in that respect [are] relatively safe. But some of the routes of administration are questionable, and there can be consequences to putting fat cells into the circulation that wouldn't normally be there. We've had patients who have had stem cells injected into the central nervous system to treat Huntington's disease or ALS come to autopsy and tumors have been found. Not invasive, aggressive tumors, but stem cells proliferating in areas where you wouldn't want them.”

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The FDA's power to investigate stem cell clinics is limited by its budget and staffing, which are already under strain. (The NEJM editorial suggests collaboration with state medical boards to extend the FDA's reach.)

“I think Europe is actually doing a better job of cracking down on these clinics than the US,” said Dr. Svendsen. “But they're slick. Every time you look, they've moved or changed their names.”

For example, the controversial German company XCell-Center, the largest such clinic in Europe at the time, shut down in 2011 after a baby died following an injection of stem cells into the brain — only to reopen later in Lebanon under the name Cells4Health. Today, Cells4Health's website lists an address in Sofia, Bulgaria.

Many stem cell clinics post dramatic videos on their websites of patients claiming miraculous improvements. “So many of the conditions they claim to treat wax and wane in their natural history,” Dr. Kriegstein observed. “If patients have a therapy that they've been told is going to work and they've invested a lot of money and energy and so on, there can be a huge placebo effect, especially initially — and that's when they make these testimonial videos.”

Proposed new stem cell guidelines issued by the FDA aiming to clarify this situation aren't sufficient, argued the researchers in the NEJM editorial. The draft guidelines stipulate that separating cells from their surrounding tissue qualifies as “more than minimal manipulation,” and that “the same surgical procedure exception applies only when the tissue undergoes minimal processing, such as rinsing, cleansing, or sizing.”

But the guidelines don't address other questions, such as whether transplanted adipose tissue must retain all of its prior functions, or only some, to qualify under 361.

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Where oversight fails, education is essential, said the experts interviewed for this article. They suggested that neurologists point their patients to “Stem Cells in Focus,” a public education site launched in April 2015 by the International Society for Stem Cell Research. The site's “Nine Things to Know About Stem Cell Treatments” section and its patient handbook provide clear, consumer-friendly explanations of the current state of stem cell science and how to assess whether a treatment is legitimate or not. The handbook is available as a PDF, so it can be printed out, copied, and distributed through any clinical practice.

“I get emails almost daily from patients who are confused and asking for guidance,” Dr. Kriegstein told Neurology Today. “They've heard about a clinic offering an unproven stem cell therapy — should they get it? There is a lot of confusion out there. I think we need to take as broad an approach to this problem as possible, including educating primary care physicians, who are probably the ones most likely to intervene before a patient tries one of these therapies.”

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The International Society for Stem Cell Research provides clear, consumer-friendly explanations of the current state of stem cell science in a downloadable patient handbook, including a glossary of terms, how to assess whether a treatment is legitimate or not, and questions to ask about stem cell treatments. Following are nine brief points the society suggests clinicians tell patients when they ask about stem cell treatments outside of clinical trials:

  1. Currently, very few stem cell treatments have been proven safe and effective.
  2. There is something to lose when you try an unproven treatment.
  3. Different types of stem cells serve different purposes in the body.
  4. The same stem cell treatment is unlikely to work for different diseases or conditions.
  5. The science behind a disease should match the science behind the treatment.
  6. Cells from your own body are not automatically safe when used in treatments.
  7. Patient testimonials and other marketing provided by clinics may be misleading.
  8. An experimental treatment offered for sale is not the same as a clinical trial.
  9. The process by which science becomes medicine is designed to minimize harm and maximize effectiveness.

These resources are also available online at

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•. Neurology Today article, “Legal Ruling Puts the Brakes on Unlicensed Stem Cell Therapies”:
    •. FDA: Minimal Manipulation of Human Cells, Tissues, and Cellular and Tissue-Based Products: Draft Guidance:
      •. A Closer Look at Stem Cells:
        © 2015 American Academy of Neurology