THE CURE – ALL ARE NEW STEM CELL THERAPIES MIRACLES IN A BOTTLE–OR JUST A DANGEROUS FORM OF SNAKE OIL?
Posted on December 29, 2015
On a snowy evening in Brooklyn, New York, sweat is streaming from my pores, rolling down my face, back, and palms. I don’t know what the temperature is here inside the MRI machine, but “summer in the Sahara” seems about right. I keep thinking about how I should have shed my winter-weight pants and button-down shirt.
The lab technician chimes in over a microphone. He reminds me not to move or I’ll need to start the MRI over. Considering I’ve been here for 45 minutes, that doesn’t sound appealing. My eyes sting, and sweat has pooled in weird places. I imagine this is what Chinese water torture feels like. Add to that, I have a gadolinium contrast agent coursing through my body. The substance is supposed to highlight areas of inflammation, but it can also make you feel like you’re itching from within.
Struggling to remain still, I try to focus on why I am here. For seven years, I’ve wrestled with back pain, a grindingly persistent condition that emanates from beneath my left shoulder blade. To fix it, I have tried nearly everything–physical therapy, exercise regimes, a standing desk, a chiropractor, a Myopractor, acupuncture. Nothing worked. The pain could be dull and nagging or acute and raging. But it was always there, no matter if I was at work, at the beach, or trying to fall asleep. I had to do something drastic. This MRI is the first step. The next will take me to the very fringes of medicine.
A week after my scan, Mark Berman calls from his office in Beverly Hills. Berman is not an orthopedic surgeon. He’s a cosmetic surgeon, a nip-and-tuck guy who, like so many others, established his practice at the center of the plastic surgery universe. Business is going so well, what with the usual face-lifts, breast augmentations, and rhinoplasties, that he maintains a second office in Palm Springs.
On the phone, Berman is chatty and affable. He announces that I have four herniated disks but none of them are near the source of my pain. In fact, he says, the MRI turned up nothing near my left shoulder blade. He can probably sense my disappointment–another dead end in a seven-year string of them–so he quickly adds, “This isn’t unusual. What we find a lot of the time is that chronic inflammation doesn’t get picked up because it’s been there so long. But you’re still a candidate.”
By “candidate,” Berman means a potential subject of an unproven surgical procedure, one without any approval from the U.S. Food and Drug Administration (FDA) or extensive scientific support. The treatment uses stem cells–undifferentiated cells that can develop into specialized tissues. In Berman’s procedure, the stem cells will come from my own fat. He claims that by circulating them through my body intravenously, they will locate sites of inflammation–whether herniated disks or torn ligaments or arthritis–and repair them. The scientific backing is shaky. There is little quantifiable evidence to defend his claim, which he freely admits. But then he points to his track record. He says he has successfully treated more than a thousand patients, and he happily gives me names and phone numbers.
One is Lamon Brewster, a former heavyweight boxing champion. In 2010, Brewster went up against the Finnish boxer Robert Helenius, a.k.a. the Nordic Nightmare. The two were pretty well matched, but Helenius had the reach. At 6’6″ he towered over 6’2″ Brewster, and in the eighth round, he landed a series of devastating hooks to Brewster’s face. Less than a minute later, the referee called the fight. A few days after that, Brewster learned that his cornea and iris were severely damaged. Within a few months, he lost all sight in his left eye.
The damage, he was told, was irreversible. Then he heard about Berman’s therapy. With nothing to lose, he gave it a shot. Months after he received stem cell injections, his vision started to return. “It’s getting better each day,” he says when I call. He also claims the benefits extend to other parts of his body: “I had boxed a long time and suffered chronic pain. But I didn’t realize I had all these issues until they started to go away after my treatment.”
“No one has proved they’re safe or effective. People are paying a lot for these treatments with no assurances.”
To someone beset with chronic back pain, the whole thing sounds too good to be true. I’ve been down the alternative-therapy road before. And I am well aware that many people view clinics like Berman’s as potentially dangerous sham operations that promise the impossible. But chronic pain can make even the most rational person irrational. As soon as I get off the phone with Berman, I book my ticket to California.
Scientists have known of stem cells since the 1950s, but the field of regenerative medicine has only really taken hold in the past 15 years or so. In that time, researchers have managed to figure out some of the basics: Stem cells appear to serve two purposes–as a foundation for all tissue in a growing embryo and as a means of repair and replacement in mature tissue. Broadly, they come in two varieties: embryonic (found only in embryos) and adult (which live throughout the body). Embryonic stem cells can differentiate into all 220 tissues in the human body. Adult stem cells typically differentiate into their tissue of origin. For example, those in bone marrow tend to grow into red blood cells, white blood cells, or platelets but not nerve cells. In 2006, researchers found a way to turn adult stem cells into embryonic ones (called induced pluripotent stem cells), but the work is new and the implications still unclear.
Berman’s procedure relies on adult stem cells. He collects a small amount of a patient’s fat, adds enzymes to digest away the scaffolding that holds the cells in place, and then uses a centrifuge to separate the components. What he collects is called a stromal vascular fraction (SVF). It’s a mix of platelets, growth factors, endothelial cells, T cells, red and white cells, and, of course, stem cells. Berman then injects that SVF back into the patient.
On a basic level, the procedure makes sense. Stem cells help repair tissues, so why not add them to damaged areas? The trouble is that beyond the basics, stem cells are far from understood. Scientists, for example, still don’t know why a given stem cell will differentiate into one tissue and not another, or what prompts cell replication to turn on or off. They also can’t predict when some stem cells will go rogue and turn into unwanted masses. Until scientists learn more, it will be impossible to say with complete confidence that any treatment comes without significant risk.
But studies are under way. In the past few years, a number of clinical trials have launched to explore cell-based therapies for strokes, spinal cord injury, and Parkinson’s disease, among other disorders. The FDA is studying eight lines of adult stem cells for their ability to repair hearts, bones, and cartilage. It also recently cleared a cell-based multiple sclerosis drug for a Phase I clinical trial. That work is encouraging, but even so, there’s a big divide between trials like these and safe, effective therapies.
Although already in use, SVF treatment has not yet bridged that gap. Berman still doesn’t understand how exactly it works, which he openly concedes. His best guess is that it’s not one factor. The stem cells in the SVF probably help repair tissue, but so do the growth factors and T cells. “These are complex processes, and we don’t have the technology to pinpoint the exact mechanism,” he says.
That’s not to say Berman is doing anything illegal by offering a treatment he doesn’t fully comprehend. He’s not. He’s not even doing anything unethical. He is healing patients who could not be healed. “People are indeed having amazing successes,” says Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine in North Carolina. But, Atala says, we need controlled studies to truly understand why. Until those happen, getting SVF is a little like gambling: You pay your money, you take your chances.
A few weeks after my MRI, I arrive for my experimental procedure at Berman’s Palm Springs clinic. After I check in, Berman joins me in the waiting room. He tells me the first step is the stock-in-trade of plastic surgeons: a little liposuction.
He walks me to an examination room and asks me to lie on my stomach. He pulls up my shirt. With a needle full of anesthetic, he numbs my left love handle–no shortage of fat there, sadly. The drug is toxic to stem cells, he tells me, so he’s careful to not inject it too deeply. Berman then makes a quarter-inch incision, inserts a small tube, and begins vacuuming. It doesn’t feel like much, a light scraping, and there’s a quiet hum. Within 10 minutes it’s over. Berman places a Band-Aid on the wound and gives the fat over to a lab tech who will render it into the SVF. In about an hour, the sample will be streaming through my circulatory system.
The procedure seems effortless. Could it be so easy to get well? Many think not.
Leigh Turner, an associate professor at the University of Minnesota’s Center for Bioethics, finds the various SVF therapies dubious. “No one has proved they’re safe or effective,” he says. “People are paying a lot of money for these treatments without any assurances.”
Paul Knoepfler, a biomedical scientist at the Institute for Regenerative Cures at the University of California at Davis, put a finer point on it: “This is a for-profit human experiment,” he says. Knoepfler maintains that stem cells could potentially form bone or cartilage in unwanted areas. He points to a case in Portugal in which a woman was treated with stem cells taken from her nose and implanted in her back to help cure paralysis. Eight years later, doctors found a lump of nasal tissue in her spine. In another case, a teenager treated at a Russian clinic with fetal stem cells for a nerve disorder ended up with a brain tumor. Neither treatment was SVF–and there is no direct evidence that SVF could lead to such results–but the risks can’t be ruled out. In one recent study in goats, SVF increased spinal inflammation and spinal disk degeneration.
“This is a for-profit human experiment.”
Despite this, Berman argues that SVF is safe. “We’ve had a thousand patients and haven’t had any significant adverse reactions,” he says. He also records his cases and says he will post them online as studies at PubMed and ClinicalTrials.gov.
A few years ago, he started something called the Cell Surgical Network, a group of about 50 doctors that includes cardiologists, radiologists, anesthesiologists, and neurosurgeons, all of whom offer SVF therapy. The more practitioners, Berman says, the more data they have.
Berman also points to the success of SVF therapy in other patients: racehorses. In the early 2000s, a company now called Vet-Stem began offering SVF to veterinarians, who can more freely use experimental procedures. One of those early to adopt it was Ross Rich, former owner of Arizona’s Cave Creek Equine Surgical and Diagnostic Imaging Center. “I was skeptical,” he says, “but I had some horses that were very expensive and couldn’t get them healed after 18 months.” Rich mentioned the treatment to his clients, and they wanted to give it a try.
“We injected the stem cells into the injured area, and three months later they were fully recovered,” he says. “I’d never seen anything like it. These used to be career-ending injuries, and now it’s like no big deal.” Vet-Stem claims to have treated thousands of horses successfully, and Rich has published studies that describe success rates of 80 to 90 percent. Plus, horses don’t experience a placebo effect. He was so convinced of SVF’s effectiveness that last spring, he and his wife got it for their back, knee, and ankle pain. Rich says they have seen dramatic improvements.
This comes as a comfort to me as I wait for my SVF to be prepared. I like the idea that a thousand people and thousands of horses have come before me incident-free. But I still have concerns. For one, most people treated with SVF received it only within the past several years. The long-term impacts of this therapy are still unknown. Also, it’s great that it has worked so well for so long in horses, but I’m not a horse.
As I sit waiting for my fat to be centrifuged, I cannot help but perform a grim calculus. What’s worse: Living another year or 10 with chronic pain or undergoing an unproven treatment? I could still back out. I could, without explanation, walk out the door, hop in my rental car, and spend the rest of the afternoon sitting poolside at my hotel in Palm Springs. All I would lose is a little fat from my left love handle (and every bit counts). Once I get the SVF injection, there is no turning back.
About an hour after my liposuction, a nurse walks into the room with a vial of my SVF. She tells me the sample contains about 50 million cells, which is normal. Most of it will be applied through an IV drip, and then the doctor will inject some below my left shoulder blade. Am I ready? she asks. I pull up my shirtsleeve and offer my arm for the IV. The needle sinks in deep. So this is what commitment feels like, I think to myself.
Almost as soon as the needle enters my forearm, a mix of stem and immune cells are coursing through my bloodstream.Because it’s unclear how the therapy works, Berman uses an IV drip to circulate the cells through the body. That way, they can attack inflammation wherever they find it. This seems a bit suspicious. Without genetic reprogramming, it’s unclear if adult stem cells from one tissue can target inflammation in another. I hope that I have not made a big mistake.
I sit with the drip for a while, and after about 30 minutes, an orthopedic surgeon named Jonathan Braslow walks in and asks about my back pain. I explain that it hovers between my left shoulder blade and my spine. Braslow seems familiar with the location and thumbs his way around until he finds the spot. “That’s it,” I say. “That’s where the pain is.”
“Okay, here we go,” he says. The needle sinks in deep. The tension in his arm releases as the SVF enters my shoulder. So this is what commitment feels like, I think to myself. Minutes later, I am out the door.
Although SVF therapy may be legal now, its future is murky. In December, the FDA released draft guidance concerning stem cells derived from adipose tissue. It was bad news for Berman. Typically, the agency regulates drugs but not surgeries. What distinguishes the two, at least in the case of biologic therapies, is the concept of minimal manipulation. If the patient’s tissue is removed and used in such a way that it retains its characteristics, that qualifies as minimal manipulation, and the procedure classifies as a surgery. If the tissue doesn’t retain its characteristics, the FDA deems it more than minimally manipulated, and the treatment is considered a drug. That means long and expensive clinical trials.
The agency’s draft guidance clearly states that stem cells drawn from adipose tissue are more than minimally manipulated. Enzymatic digestion and separation by centrifuge leaves doctors with something very different from plain old fat. According to Turner, the bioethicist at the University of Minnesota, the FDA position is a strong signal of coming regulation. But when that will arrive is anyone’s guess. For now, SVF clinics are in the clear. “Draft guidances are not legally enforceable,” he says. “If you were to extrapolate from the past into the future, I’d say we’re going to see more of these clinics.”
When I reach Berman by email after the FDA announcement, he’s unfazed. “The entire purpose of the FDA mandate is to prevent the transmission of communicable disease,” he writes. “Since everything we use is FDA-approved, even if not approved specifically for making SVF, as surgeons, we can do whatever we want as long as there’s no risk of disease transmission.”
While things get sorted out, Berman says, the Cell Surgical Network is building a cryogenic library where patients can store stem cells, much like women store reproductive eggs. As we age, we lose stem cells. Wouldn’t it be nice to dip into a stock of frozen ones to save a limb or stave off crippling arthritis? “I think transplants will be a thing of the past,” says Rich, the veterinarian. “In the future, you might be able to call a company that has the best stem cells for the damaged body part and have them overnighted.”
A week after my SVF, I’m at home working when I realize that, for the first time in seven years, I have no back pain. I just feel normal. On various stem cell–related sites, I’ve seen plenty of warnings that improvements to a condition may not be the result of a stem cell treatment. Relief can come from some mixture of the placebo effect, concurrent therapies, and natural healing. But I hadn’t had a placebo effect from any of my other treatments, I haven’t been doing any other therapies, and I hadn’t healed naturally in seven years.
I realize that, for the first time in seven years, I have no back pain.
Then I drive from New York to Maine. Long drives were always my Kryptonite, and sure enough, by the third hour of the six-hour ride, I can feel my old pain begin to return. I try not to think about it, but it is there. I feel defeated, and I call Berman a few days later. He tells me to stay positive. “Sometimes it will come back a bit and then go away again,” he says. “You just have to give it some time.”
Slowly, the pain subsides. While it pops up every now and again, it disappears just as quickly. Then, about three months after my treatment, it seems destined to never return, no matter how long I drive or how much I exercise. It’s just gone.
At this point, it’s been nearly a year, and I’m pain-free. Still, I worry that it’s all just temporary. I recently heard from Lamon Brewster, the boxer. He said his recovery had inexplicably failed, leaving him blind in his left eye once more. “It just reversed,” he says. While Brewster is the exception and not the rule among the SVF patients I’d spoken with, his case is an important reminder of something I try not to think about too much: When you sign up to be a guinea pig, nothing is certain, and only time will tell.