Senator Sherrod Brown was hosting a morning coffee with constituents and taking questions on a range of hot-button topics when Hamilton County Coroner Lakshmi Sammarco, M.D., raised her hand, changed the subject, and asked pointedly whether there was movement around regulating stem cell treatments. The U.S. Food & Drug Administration, she noted, had issued warnings concerning treatments that were not FDA-approved but still being offered throughout the country and here in Ohio, in some cases leading to dangerous side effects. For his part, Brown was unfamiliar with the issue and said he’d look into it.
When I ask Sammarco why stem cell treatments concern her, she mentions that a friend of hers had spent around $60,000 on these treatments, traveling abroad to get them. Sammarco is aware of neurosurgeons offering stem cell treatments and other physicians claiming they can treat everything from blindness to back pain. “I’m pretty sure there are no long-term studies to show any of this to be the case,” she says.
A simple internet search about stem cell treatments yields a screaming debate. Warnings on Consumer Reports and PBS. A Washington Post story, “ ‘Miraculous’ Stem Cell Therapy Has Sickened People in Five States,” details how one company sold vials of umbilical cord blood solution contaminated with E. coli. A woman in Georgia went blind after receiving an injection of stem cells to treat her macular degeneration. Others suffered kidney failure and lower body paralysis. A Cleveland TV station’s hidden-camera exposé tracked sales pitches in restaurants and conference rooms where chiropractors told rooms full of mostly senior citizens that stem cell injections could treat back, hip, knee, and shoulder problems. One bioethicist the Cleveland news team interviewed called the stem cell treatments “snake oil.”
Despite the negative outcomes, these treatments are gaining popularity, with growing legions of former patients posting testimonials online. One count in 2017 found 716 clinics throughout the U.S. offering stem cell–based interventions; at least half a dozen clinics in the Cincinnati area now do them.
Web sites touting regenerative medicine—cell therapies treating or healing a person’s damaged or diseased tissues—and related stem cell treatments are littered with amateur YouTube videos of people describing alleviated back pain or no-longer-necessary knee replacements. One local clinic, StemCures, links to a quote from FDA Commissioner Scott Gottlieb in a 2017 news release describing “novel cellular therapies,” saying, “This is no longer the stuff of science fiction. This is the practical promise of modern applications of regenerative medicine.”
Yet if you follow the related links at the bottom of that FDA news release, you’ll find a new FDA warning about unapproved stem cell therapies posted in September 2019. At the top of the warning page, the FDA’s embedded video begins: “Have you seen ads or attended a seminar for stem cell therapies that claim to be able to treat diseases like chronic joint pain, Alzheimer’s, cancer, and more? Don’t believe it.” To further underscore the danger, and with ominous synth-Muzak trilling a “patient beware” melody, the FDA’s message continues: “You may be told stem cells, including those from fat, amniotic fluid, or umbilical cord, like cord blood or Wharton’s Jelly, are a miracle treatment. You may even hear they are FDA-approved. But that is not true. None are proven to work to treat these conditions, and worse, some may cause harm.”
So why are people willing to seek and receive these therapies? Often, they’re sick or in pain. They find message boards or Google reviews from other patients online about how much stem cell treatments helped. They see videos—some taken on a doctor’s cell phone—of people just like them posted on a clinic’s web site, people who were willing to try something experimental and now feel better.
Maybe a physician told them it might help because it’s helped other people. And to be fair, there are populations of patients now who have had these treatments and who tell their doctors they do feel better, so the doctors hear anecdotal evidence that convinces them continuing to offer the treatments is the right thing to do.
When you’re desperate for a medical cure, that bright line of hope and the promise of advanced science are enough to get many to take a leap of faith—and pay thousands out of pocket to do so.
Every part of your body—your organs, your muscles, your aching back—can be traced back to embryonic stem cells that differentiated, using what was coded in your DNA at conception to create the various tissues that make up your body today. At one point in your body’s development, those stem cells could have become any cell type.
Since scientists learned how to derive embryonic mouse stem cells nearly 40 years ago and grow stem cells from human embryonic tissue starting in 1998, a field of research grew up questioning whether stem cells—with their vast potential to become any cell in the body—could be “reprogrammed” to treat the most puzzling ailments, such as cancer or degenerative neurological diseases. Ethical questions were raised immediately, too, as the early studies depended on leftover embryos donated after in vitro fertilization.
Can adult stem cells be used to make replacement healthy cells and fix what’s broken in a sick body? If the answer is yes, it could represent a revolution in medicine.
In recent years, another arm of stem cell research has sidestepped some of the ethical questions around embryonic research, chemically reducing blood and skin cells in the lab to their undifferentiated state, at which point they can then form any of 200 cell types. These induced pluripotent stem cells (iPSC) are at the vanguard of stem cell research and can be used to grow tissue or organ cultures in the lab. Picture scientists using these organoids to study how medications work on human tissue instead of animals, or ultimately using lab-grown tissues in transplant surgeries. It’s not possible yet, but something scientists as close as Cincinnati Children’s Hospital Medical Center are working on.
That cutting-edge science has kept the promise of stem cell research in the news, but the treatments sweeping the nation aren’t derived from embryonic or iPSCs. There’s a third category, “adult” stem cells, that still hold the potential to become a variety of other cells and can be extracted from bone marrow, blood, or fat cells. We carry around a relatively easy-to-access supply of those cells, and with so much promise on other fronts in stem cell research, a new question seems to be driving a growing number of physicians and patients: Can adult stem cells be used to make replacement healthy cells and fix what’s broken in a sick body? If the answer is yes, it could represent a revolution in medicine.
But there’s a raging debate within the medical community around whether we are, in fact, witnessing that revolution or whether some physicians—hawking the perhaps not-yet-achieved promise of stem cell treatments—are offering said treatments, with little scientific evidence of their efficacy or safety, to patients desperate for help who don’t fully understand the limits of the current research.
What further complicates things is that some clinics have web sites or seminars that make blanket statements about years of stem cell research, which strictly speaking is true—various aspects of stem cell research have been going on for years. “But research for what reason?” Sammarco asks, adding that the research is relevant only if it demonstrates an ability to cure or treat a patient’s specific disease.
Part of what’s tricky here is the definition of certain words. Is something experimental because it’s simply not well-tested or because it’s in the process of being tested rigorously? What does it mean—as these treatments are often described on clinic web sites—if something is not FDA-approved but is FDA-compliant?
Medicine and treatments the FDA approves go through a rigorous, evidence-based review process. Depending on how they’re used, stem cells can be classified as drugs, biologics, or medical devices, which would require FDA premarket approval, an FDA investigational new drug application, and studies approved by an institutional review board. Bone marrow transplants, which are FDA-approved, are used to replace blood cells destroyed during chemotherapy. These newer stem cell therapies, however, are not approved. Bone marrow or fat cells are reinjected into various body parts in hopes of regenerating new, healthy cells. But the research on these treatments is terribly thin. Yet many of the clinics offering stem cell treatments call themselves “FDA-compliant.”
A procedure might be FDA-compliant, meaning it doesn’t break any of the FDA’s rules around infectious disease or what can and can’t be injected into the body, but that’s not the same as going through a scientific review to demonstrate its efficacy, which precedes FDA approval. It’s a fine distinction. The former means your clinic handles tissues safely; the latter would mean the treatment showed itself to be effective through years of requisite scientific study.
So long as those cells aren’t contaminated or manipulated, you’re free to try it. And, for some patients, the treatments seem to work. One man, who I’ll call Doug (he has a public-facing job and would rather keep his medical treatments private), had his knee scoped three times for torn cartilage. “It never did get really better. I still had pain,” he tells me. Once his other knee started acting up and X-rays showed he’d need knee replacements, he was worried. What if surgery didn’t work? A friend of his had a knee replacement, and it took nearly six months for him to recover.
Doug, who is 67, had heard about stem cell treatments and started researching. “The jury is still out on stem cells,” he says. “I mean, each article you read, one’s for, one’s against.” He went to a two-hour seminar offered by Elite Physical Medicine in Mason, where he was given examples of former patients who swore by the treatment. He figured What have I got to lose, other than a few bucks? because while his health insurance would have covered a knee replacement, he had to pay for the $14,000 stem cell treatment himself. Doug’s course included four injections: the first a stem cell injection, and the next three platelet-rich plasma. His doctor warned him it could take six months before he’d see a big difference—but to his mind six months of slow improvement seemed better than a six-month recovery from knee replacement.
So far, Doug says he’s less stiff in the morning. Before the treatments, he was taking ibuprofen twice daily for pain. Now he doesn’t need to take any.
Leigh Turner, a medical ethicist at the University of Minnesota’s Center for Bioethics, has written extensively about stem cell treatments. He points to a study by Mayo Clinic orthopedic physician Shane Shapiro, published in The American Journal of Sports Medicine, of 25 patients suffering with arthritis pain who were given an injection of a stem cell treatment (bone marrow aspirate concentrate) in one knee and a saline placebo in the other. The patients didn’t know which knee received the stem cell treatment. Patients reported that not only did their pain decrease significantly in the knee given stem cell treatment, but the knee injected with saline also felt better. No adverse effects were noted.
Shapiro concluded that the study indicated the treatment was safe and could relieve pain. While it couldn’t yet be conclusively recommended for routine arthritis care, he wrote, the findings should be studied further as “bone marrow stem cell injection in one ailing knee can relieve pain in both affected knees in a systemic or whole-body fashion.”
Turner, though, instead notes that the intervention didn’t beat the placebo effect. The untreated knee might have felt better for the same reason the treated knee did: the psychological benefit of being treated at all. “Is that what’s happening at a lot of these businesses? That people are having an intervention, they’re convinced that it’s helping them, and that’s basically all there is to it?” He adds, “It’s kind of like medical theater.”
I first meet Jeremy Girmann, D.O., at a West Chester Starbucks. Blond, blue-eyed, with a sparkling smile, he’s often featured on Inertia Medical’s Instagram page referring people to company-branded joint treatments and protein supplements. I’ve also seen him listed as a physician at another clinic, Renew Medical, where his partners are twin brother chiropractors Paul Baker, D.C., and Patrick Baker, D.C., both of whom say they received stem cell treatments from Girmann that left them “amazed at how well it worked” and “100 percent better,” respectively.
Meeting Girmann, I expect a sales pitch. He instead first wants to clarify the limits of stem cell research and treatment. He underscores that he’s not working with embryonic stem cells, but rather adult stem cells. He focuses on a variety of regenerative treatments, including one type of adult stem cell, Mesenchymal Stem Cells (MSC), which maybe shouldn’t even be called a “stem cell.” MSCs have the ability to renew and differentiate into bone, cartilage, muscle, and fat cells. Girmann says the biologist who popularized MSCs, Arnold Caplan of Case Western Reserve University, wrote an editorial in Stem Cells Journals in 2017 saying Mesenchymal Stem Cells should instead be renamed Medicinal Signaling Cells.
“Instead of converting into all these different cell types” as embryonic stem cells can do, says Girmann, MSCs “secrete a number of growth factors and healing chemicals and medicinal molecules that then allow for a coordination of the healing process.” Hundreds of companies have formed in recent years to exploit their regenerative, healing properties instead of inducing them to form into a variety of tissues. “Unfortunately, the fact that MSCs are called ‘stem cells’ is being used to imply the patients will receive direct medical benefit, because they imagine that these cells will differentiate into regenerating tissue-producing cells,” he says.
MSCs are readily available in adult fat tissue or bone marrow. If Girmann injects the knee of a patient with MSC, he says smaller case studies and his own experience show that “patients do seem to get a certain benefit. The reason for that, we’re still working out.” MSCs, he says, become activated in the body and release molecules that help heal, for example, a wound. By far and away, he thinks “the biggest reason in which some of these treatments are exerting benefits is from the molecules they secrete rather than by becoming a whole bunch of different cartilage cells and that sort of thing.”
In other words, it’s not likely that MSCs are behaving like embryonic stem cells would and becoming a new type of cell. Girmann believes they’re simply doing the healing work these cells do elsewhere, in a directed way where they’re injected.
Girmann says he prefers to start a discussion with patients about other treatments, such as platelet-rich plasma or growth factor allografts (tissue grafts), depending on their symptoms and what shows up on ultrasound. For some, surgery is a better option.
In other countries where the FDA’s rules don’t apply, a patient might have bone marrow taken, grown in a culture for a week or two, and be reinjected with 1,000 times the number of cells extracted. Here, Girmann extracts a person’s own bone marrow, runs it through a centrifuge to separate the MSCs, and reinjects a concentrate of the patient’s cells into the injured area.
For Girmann, “when you say ‘stem cell therapy,’ at least as it applies to what I do, it means a regenerative treatment and potentially healing treatment, reducing symptoms and optimizing joint health.” But what’s frustrating to him, trying to navigate a system where research is sparse and patients need help, is “shady things” like “providers making claims that stem cell therapy can help you, you know, cure MS or Parkinson’s. That is how you start to make a whole industry that has a lot of promise look really bad.”
Girmann voices frustration over the lack of large-scale studies. The company Regenexx, which manufactures a system for accessing bone marrow, does have a patient registry, “but you have to take all that with a grain of salt,” he says, “because here are patients who have paid for a procedure.” All of the patients know what they paid for, so it’s not double blind or randomized. “It’s frustrating as providers because, especially those of us who are science-based, we want to have that data.”
Sammarco, who remains unconvinced that there’s sufficient data to define what exactly, if anything, is occurring during stem cell treatments, notes how often the people who seek this treatment are particularly vulnerable, in pain, and desperate. “I don’t really have an issue with people who are legitimately trying these things, and it’s not too expensive for the patient,” she says. But the pricing for some treatments—like the one her friend had, at $12,000 out of pocket per injection—is ridiculously expensive and comes with big promises and little accountability.
Brian Grawe, M.D., specializes in orthopedics and sports medicine at UC Health. He does research in association with stem cell treatments, but he too clarifies that it’s “a therapy in terms of the advantages of growth factors and cells, but true stem cell [treatments] where you manipulate the tissue and stuff like that, that’s not really occurring in a lot of places.” The distinction is confusing for patients, he says, and that’s part of the problem. “You have a lot of patients coming in wanting a sort of ‘Hail Mary’ for a number of disease processes,” hoping stem cells will be right for them, even though “stem cell treatment” means a lot of different things.
Grawe meets patients who want organogenesis—when a stem cell turns into something else. That process has to be guided and careful. You wouldn’t want, for example, an injection in a muscle turning into bone. “Blindly injecting a lot of these things or utilizing these things does not always come without consequences,” he says. He too takes bone marrow, rich in growth factors (that’s why when you break a bone it can heal nicely and regenerate), and injects it into the injured area.
But since there is so little regulation around these treatments and no licensure associated with it, a patient can have a difficult time knowing which physicians have medical training in the procedure and which are simply out for profit. For his part, Grawe has participated in various not-yet-published multi-center trials. The stem cell treatments he offers are used to augment healing in conjunction with another procedure—for example, meniscus or complex tendon repairs. “I’m already doing something that’s tried and true, and then this is additive,” he says, adding that patients are charged only for the cost of the stem cell kit—a few hundred dollars—rather than the thousands he knows some charge for the treatments. “That’s how we feel comfortable doing it from an experimental standpoint. We’re not charging the patient any extra money.”
It’s one of those weird and mercilessly hot fall afternoons, and Renew Medical is offering a seminar about regenerative medicine: a slideshow in a small lecture hall about platelet-rich plasma, growth factor allografts, acid gel injections, and autologous stem cell therapy (“autologous” meaning cells obtained from the same individual). On my way in, the receptionist hands me a Renew Medical pen with the clinic’s number, 561-STEM. The lobby is heavy with the scent of eucalyptus.
In the lecture space, the audience consists of three men with silver hair, a man a decade or so younger, and a man and a woman hoping to learn about treatment options. Girmann is at the front synopsizing much of the same information he told me over coffee. He highlights that he’s not just injecting willy-nilly but using ultrasound to target injections at a point of injury. Also, that stem cell treatment isn’t covered by most insurance plans.
As the audience asks about outcomes, Girmann rattles off a range. Those who feel better do so month over month, then eventually plateau. For some patients, feeling 80 percent better is enough to get on with life. Some patients will come back for follow-up treatment and their X-ray will show little physical change, but they say they feel great.
A taller man in the audience asks about intravenous injections. Girmann says that “people are doing all kinds of wacky things, and I think we’re just not there yet with the science.” He’s most comfortable focusing on orthopedic care and joint treatments. The audience member says he’s read about a 90-year-old man getting stem cell treatments for a bad hip with a stunning list of other improvements to vision, prolapsed heart valve, and erectile dysfunction.
At the end of the talk, Girmann’s medical partner Paul Baker steps up to explain that everyone attending that day’s session gets a $49 one-hour consultation with their doctors to see if they’re candidates for one of the treatments. “What does that include? That includes a history—a thorough history—an examination, and any and all X-rays for just $49,” he says.
Baker describes how he’s had five treatments himself in his hip, shoulder, and knee. He’s been a wrestler and a body-builder, and today is a stocky model of health in a room of patients with aching joints. “I’m getting regenerative treatments in my 50s, because, no offense, I know how my patients look when they are 70, 80, and 90,” he says. “I don’t want to be that person.” The tall guy in the audience asks Baker how he feels. He says he lifts weights six days a week and his body feels very young—something he didn’t feel before regenerative treatments.
On the way out, I drop the branded pen back in the cup at the front desk as audience members line up to schedule their $49 consults.