Stem-cell therapy, with a growing market, comes under a microscope

State regulators have disciplined an Edina pain specialist for his promotion of stem-cell treatments, casting new light on a growing controversy over use of the therapies for everything from joint pain to vision problems despite limited oversight and proof that they work.

Dr. Matthew Thorson was reprimanded late last year after the Minnesota Board of Medical Practice received complaints that his Stem Cell Centers of Minnesota practice made marketing claims that haven't been proved in research and paid recruiters per patient they steered to his clinic.

But Thorson is hardly alone in this new, direct-to-consumer frontier in health care.

"Regenerative medicine is not going anywhere," he said.

As many as 13 clinics in Minnesota and hundreds nationally provide therapies that pledge to use the regenerative qualities of stem cells, even though the therapies haven't gone through the same rigorous federal approval as prescription drugs.

Minnesota's providers range from independent practitioners such as Thorson to the Rejuv clinics in Savage and St. Cloud that partner with Regenexx, a Des Moines-based national stem-cell company. Mayo Clinic and Twin Cities Orthopedics (TCO) have gotten into the market as well.

In an interview, Thorson acknowledged marketing mistakes by an agency that he no longer employs, but said the stem-cell injections and other forms of regenerative medicine he offers are at least safe. They also have reduced pain, increased mobility and prevented or delayed surgery for many of his patients, he said, even if medical research on those benefits is limited.

"If you have a low-risk, potentially high-reward procedure, why would you not offer that?" said Thorson, who also is part of the Advanced Spine & Pain Clinics practice.

Scrutiny of this industry has increased in recent years. The U.S. Food and Drug Administration won what its director called a "must-win case" last summer against Florida-based U.S. Stem Cell, whose fat-derived stem-cell products were implicated in causing blindness in four patients. The FDA this fall issued warning letters to 20 providers making excessive or unproven claims about their therapies.

The surprise to some is that the industry has only grown, despite these warning shots from regulators.

"You might sort of think, 'OK, this is a market that is going to shrink now that authorities have caught on.' Instead I'm seeing the opposite," said Leigh Turner, a University of Minnesota bioethicist, whose 2016 report on the market for unapproved stem-cell treatments spurred federal regulators into action. "It doesn't seem to be having any kind of significant effect on the marketplace as a whole."

The direct-to-consumer stem-cell therapy market has emerged amid growing interest in alternative therapies, and even some skepticism toward mainstream medicine after some physicians fueled the opioid epidemic by overprescribing for pain.

There is little doubt about the regenerative and therapeutic potential of stem cells, the so-called master cells that are capable of growing other cells and tissues in the body. The U's Stem Cell Institute has demonstrated the power of these cells through research. Hospitals and cancer centers routinely use stem cells obtained from patients' own bone marrow to treat cancers and blood disorders.

The growing direct-to-consumer stem-cell market includes autologous injections, in which patients receive treatments using their own stem cells, and allogeneic injections, in which patients receive mass-produced stem-cell products derived from sources such as umbilical cord blood or amniotic fluid that is left over from childbirth.

Many providers offer other types of cellular therapies as well such as injections of platelet-rich plasma, taken from patients' own red blood cells, to stimulate healing.

A key standard for the FDA is whether stem-cell therapies are produced with minimal manipulation — which means that the fundamental properties of the cells aren't altered in the process. Any products that exceed this standard require specific FDA approval, because altered cells can be unpredictable and raise risks of cancer formation.

Thorson mostly offers autologous procedures — obtaining stem cell-rich bone marrow from patients, spinning the cells in a centrifuge to concentrate them, then injecting them back to the site of an orthopedic injury.

Mayo and TCO offer this type of therapy as well, which doesn't alter the cells and isn't subject to FDA approval.

The decision to add the therapy in 2018 was controversial for TCO, said Dr. Gary Wyard, the group's chief medical officer. In addition to the lack of evidence of effectiveness, he said there are no guidelines about the proper dosage, frequency or injection site.

"It's the Wild West basically," he said. "There were a lot of doctors who didn't want to touch it."

Mayo sought proof of effectiveness through a randomized clinical trial — giving arthritic patients stem-cell injections in one knee and non-medicating saline injections in the other. Neither doctors nor patients knew which knees received the stem cells. The trial failed to prove effectiveness because patients saw equal levels of improvement in both knees.

Even so, Mayo still offers the therapy, which is probably suitable for middle-aged adults who won't benefit from physical therapy alone but aren't ready for joint replacement yet, said Dr. Shane Shapiro, medical director for Mayo's regenerative medicine program at its Jacksonville, Fla., campus.

"We try and counsel patients on the best treatment options," he said. "We really don't push these treatment options at all."

While some manufacturers of off-the-shelf stem-cell products have argued that their products don't require FDA oversight either, Shapiro disagreed and said he won't consider them until they receive federal review.

The FDA cited a California company last year for selling umbilical cord-produced stem-cell products that resulted in life-threatening blood infections for 12 patients. It also has given manufacturers until November to disclose details of their products so it can determine whether they must be regulated.

Health insurance generally does not cover these procedures, though Regenexx has reached direct contracts with some employers such as Hy-Vee to have their patients try stem-cell therapies before orthopedic surgeries.

Autologous procedures cost $4,000 to $7,000 in Minnesota, meaning they are far cheaper than orthopedic surgeries — as long as they prevent the need for those surgeries.

Blue Cross and Blue Shield of Minnesota declined to cover stem-cell therapies for orthopedic issues and for peripheral arterial disease after reviewing the medical evidence this year and finding the therapies to be experimental.

That leaves patients paying the full cost, which bothers bioethicist Turner because those desperate for pain relief can spend thousands and potentially receive no benefit. "I see the potential for financial scams to prey on genuine suffering," he said.

Thorson said he believes it's only a matter of time before the research catches up with the as-yet unproven benefits of stem-cell therapies. Like Mayo and TCO, he is engaging in research to produce some of that proof.

As a result of the sanction against him, Thorson agreed to a $13,351 fine, to refrain from false advertising, and to provide informed consent to patients about the pros and cons of regenerative medicine.

Thorson said he is an advocate for more oversight, and encouraged the state's providers, insurers and policymakers to work together to come up with best practices in the field.

He said he has declined stem-cell therapies for numerous patients, including one seeking it for a heart problem, and urged standard treatments.

"Some people think this is a fountain of youth," he said. "That's not what it is. Whenever we market it and talk to patients about it, we need to be really clear about that."