Across the United States and in at least one Canadian city, people are paying thousands of dollars for an unproven, same-day stem cell treatment to ease pain and restore flexibility in their arthritic or damaged knees.
The question is: does it work?
“We don’t have any really good, level one evidence out there yet,” says Dr. Shane Shapiro, an orthopedic surgeon at the Mayo Center for Regenerative Medicine in Jacksonville, Florida. “But judging by the proliferation of practices that perform the procedure and the number of patients that have it, many people are willing to jump in without knowing whether it will or won’t work.”
Dr. Shapiro leads a 25-patient clinical trial investigating whether the bone marrow aspirate concentrate (BMAC) procedure actually relieves pain and helps knees heal in patients with osteoarthritis. Over the past three years he and a team of researchers extracted mesenchymal bone marrow stem cells from patients’ pelvises, spun them in a centrifuge to a concentrated state and then re-injected them into one knee. The other knee, serving as a control for the experiment, got a placebo injection of saline solution. Patients then underwent magnetic resonance imaging (MRI) at six months and a year to see if the knee cartilage improved from its original inflamed state.
Mesenchymal stem cells are used because they can differentiate into bone cells, cartilage cells and muscle cells. They also have anti-inflammatory qualities, which could be helpful in treating osteoarthritis. The process is considered “autologous” because the cells are reinjected into the same person who provided them, as opposed to “allogenic” transplants that involve cells donated from another person.
Dr. Shapiro expects the results to be published soon. Meanwhile, clinics offering the BMAC procedure are popping up all over and charging between $1,800 and $10,000 per injection. ”Unfortunately, now you can take a weekend course or four-day course in how to do this,” says Dr. Shapiro. “I actually don’t think that all places that you can get this done are reputable, but there are some.”
What does the FDA say?
The U.S. Food and Drug Administration (FDA) has published draft guidance documents that reflect the agency’s current thinking about such treatments. At issue is whether the procedure constitutes more than “minimal manipulation” of the cells based on the degree of processing they undergo, and represents “homologous use” — meaning the cells perform their same basic function at the site in which they are injected. The draft guidance seems to indicate the BMAC procedure meets the criteria of minimal manipulation and homologous use,
When we sought clarification, the FDA’s Center for Biologics Evaluation and Research wrote in an email that it “expects anyone involved with human cells, tissues, and cellular and tissue-based products (HCT/Ps), including stem cells, to familiarize themselves with the regulations; they are responsible for self-assessing how the appropriate regulations apply to their products.” It added that the attributes of “processing/manipulation and intended use must be carefully evaluated on a case by case basis.”
Health Canada, which takes a harmonized approach to that of the FDA, has not yet considered whether BMAC meets minimal manipulation or homologous use criteria. According to a statement from the Biologics and Genetic Therapies Directorate, “In some cases, autologous cell therapy products that are processed for a particular patient by a regulated health professional pursuant to the scope of their practice may not require federal pre-market regulatory authorization under the Food and Drug Regulations.”
In 2014 the U.S. Federal Appeals Court ruled in FDA’s favour in a case against Regenerative Sciences, a Colorado-based organization that until 2010 had been offering the BMAC treatment with cells that were extracted, cultured to make them more robust, and then re-injected into the patient. The organization now offers the treatment — called Regenexx-C (for “cultured,” a process that takes several days) — only at a clinic in the Cayman Islands, beyond the FDA’s jurisdiction. They continue to offer Regenexx-SD (for “same day”) at the Centeno Shultz Clinic in Colorado and at a network of clinics around the United States.
At a recent webinar, Dr. Christopher Centeno said that while “there are some additional regulations that may be coming out on stem cell therapies,” he didn’t anticipate that “any of those are going to change what happens here at Regenexx” and added that “right now there are no FDA guidelines for this type of work.”
The BMAC procedure should not be confused with stromal vascular fractioning (SVF) in which adipose (fat) cells are drawn from a patient by liposuction, run through a centrifuge to isolate the stem cells and then re-injected into the patient’s damaged knees or hips or shoulders. In fact, many clinics offer the treatment for a laundry list of conditions and diseases. Because SVF breaks down and eliminates the structural components of the adipose cells, it goes beyond the limits of minimal manipulation, according to the FDA. The agency has begun cracking down on clinics offering the procedure.
Here in Canada, clinics are offering BMAC procedures, says Dr. Jas Chahal, an orthopedic sports medicine surgeon with the Women’s College Hospital and the University Health Network in Toronto. “You can get it done. I’m not sure if you can get it across Canada, but there are people doing it in the Greater Toronto Area, for sure.”
Canadian study goes beyond BMAC
Dr. Chahal says more study is needed to prove whether the BMAC procedure is effective. “If you look at some of the articles presented at conferences, the basic science evidence shows that there could be a benefit — there are some anti-inflammatory molecules in there and there are some growth factors. I just don’t think it’s been adequately studied.”
Dr. Chahal and his team are midway through conducting a clinical trial that goes well beyond the same-day BMAC procedure. They are extracting the mesenchymal bone marrow stem cells from their patients and doing ex-vivo expansion (ramping up the number of cells in a lab) and then re-injecting them at concentrations of 1 million, 10 million and 50 million cells. “We’ve enrolled 12 patients and treated six so far,” says Dr. Chahal. “We expect to treat the next six in the next six months and should have data in another year.”
Should the Mayo Clinic study show positive results, Dr. Shapiro expects it could take some time for the BMAC procedure to become standard treatment for osteoarthritis. For one thing, there’s the cost.
“Someone has to pay for this,” says Dr. Shapiro. “If you’re going to be delivering it to millions of people, it has to come down in cost. It’s got to be more efficient and there’s got to be a system where it’s covered under either public or private health insurance, so that we could deliver it to the large number of people who need it.”