e are witnessing great promise in medicine today. The vocabulary dazzles: “precision medicine,” “stem cells,” “moon shot,” and other terms that hint at exciting new possibilities. But it is also a time of great vulnerability for patients.
I’m particularly worried about stem cells or, more precisely, stem cell therapies. In theory, stem cells could help treat — or even cure — conditions ranging from cancer to heart failure. As a cardiologist, I’m especially interested in their application to the latter condition. Even though the hype far exceeds the evidence, patients are already turning to so-called stem cell clinics that claim to reverse heart failure.
So-called “pluripotential” stem cells have the ability to develop into different cell types. They can be derived from various sources, including a patient’s own blood, fat tissue, and bone marrow, or from a donor, as with umbilical cord blood. Stem cells can be mobilized and directed to target sites by infusing them into a vein or artery or even directly injecting them into a particular organ or tissue.
For several years, researchers have explored how stem cells might be used to treat a variety of conditions, including spinal cord injury, burns, diabetes, and systolic heart failure. In heart failure, impaired contractility of the heart muscle makes it difficult for the heart to pump enough blood to meet the demands of the body. The hallmark symptom is shortness of breath on exertion. Other common symptoms, many of them related to the buildup of fluid in the body, include swelling in the abdomen and lower extremities.
The idea is that stem cells added to a failing heart will grow into healthy heart muscle cells or possibly form some sort of supportive cellular scaffolding and reverse the decline. Yet there’s substantial uncertainty about the effectiveness and durability of stem cell therapy, which may depend on the type of stem cells used, the quantity administered, and the way in which the cells are delivered.
A recent trial by Joshua M. Hare and colleagues that hints at the benefits of stem cell therapy for heart failure represents one of the best designed studies to date, but with just 37 patients enrolled, it does not carry the same weight of evidence that emerges from randomized controlled trials with thousands of patients. It isn’t clear where the regulatory bar lies at the Food and Drug Administration, in part because stem cell therapy is a novel approach and, as a consequence, it is reasonable to have concerns about potential short- and long-term adverse effects.
Yet despite the great uncertainty about the value of stem cell therapy, direct-to-consumer stem cell centers have opened in the U.S. and abroad. These businesses advertise and promote treatment for patients desperate to get on the stem cell bandwagon but exist without regulation, monitoring, or peer review of results. In an effort to gain credibility, some of them have found ways to list their “studies” on clinicaltrials.gov (the U.S. National Library of Medicine’s database of privately and publicly funded clinical studies conducted around the world) even though they are not, in fact, studies. They often engage in hard-sell marketing tactics.
Several colleagues and I surveyed 30 stem cell clinics offering treatments for heart failure. As we wrote in a research letter published in JAMA Internal Medicine, the picture wasn’t pretty. The medical expertise was limited: Of the 79 physicians we were able to identify working at stem cell clinics offering treatment for heart failure, only one was board certified in cardiology. Ten had no formal medical training, but were instead described as “naturopathic medical doctors.”
These centers rarely discussed the potential risks of stem cell therapy. Only nine of them required patients’ medical records before beginning treatment. In most of the centers, stem cells were harvested from fat tissue and were delivered intravenously (through the bloodstream), though without careful monitoring it is impossible to know if the infused stem cells got to the heart or if the patients were even receiving stem cells.
The average cost for “stem cell therapy” for heart failure in the 30 centers was more than $6,000. Some of the centers offered a discount for payment in cash, or for having additional procedures. Since none of these procedures are FDA approved, there is no third party reimbursement — the patient must pay in full.
The FDA at long last has taken some steps to curtail the practice, but one could ask the agency: What took you so long? In a clinical trial, if a patient sneezes, clinicians find themselves filling out adverse event forms. But you can still walk into a stem cell business on Main Street and buy yourself an infusion with virtually no oversight from the medical community or state or federal governments.
Conventional treatments for heart failure don’t always work, and the condition can get progressively worse. Advocates might argue that patients who don’t benefit from conventional treatment should be offered the opportunity to try something novel.
As an investigator in several gene therapy trials for heart failure, I learned that patients with chronic symptomatic conditions are very willing to take chances on potential high-tech solutions. It is almost certainly a reflection of the worry and desperation that many people with heart failure have, and that we as providers underestimate. I recall talking with patients who were thinking about participating in gene therapy trials and noted their distress when they realized that randomization to placebo was possible — even though we explained that there was uncertainty as to whether gene therapy would be helpful, neutral, or harmful.
So I’m not surprised that patients are vulnerable to stem cell hype and, in the right setting and with the right economic resources, find their way to commercial stem cell businesses.
I’m not an FDA official, nor do I have the ear of one. So all I can do is advise my patients about what I believe is the best way forward: If you are interested in stem cell therapy, volunteer to enroll in a legitimate clinical trial rather than take on the risks associated with an unregulated business.
To me, the stem cell imbroglio is just one facet of a health care system that seems at times to have deviated from its mission of putting the interests of the patient first. With a dose of political will, we can reverse a permissive attitude toward off-label commercial stem cell infusions.
Paul J. Hauptman, M.D., is professor of medicine and assistant dean for clinical and translational research at Saint Louis University School of Medicine. He has financial relationships with several pharmaceutical and medical device companies, but none in the stem cell space.