Posted 30 April 2018
Miracle cures or modern quackery? Stem cell clinics multiply, with heartbreaking results for some patients.
by Laurie McGinley and William Wan
Washington Post April 29
Doris Tyler lay on the examining table as the doctor stuck a long, thin tube into her belly. The doctor pulled back a plunger, and the syringe quickly filled with yellow blobs tinged with pink.
“Look at that beautiful fat coming out. Liquid gold!” one of the clinic’s staff exclaimed in a video of the procedure provided to The Washington Post.
Hidden in that fat were stem cells with the amazing power to heal, the Stem Cell Center of Georgia had told Tyler. The clinic is one of hundreds that have popped up across the country, many offering treatments for conditions from Parkinson’s disease to autism to multiple sclerosis.
Federal regulators have not approved any of their treatments, and critics call such clinics modern-day snake-oil salesmen. But on that day in 2016, Tyler trusted the clinic to extract stem cells from her fat and inject them into her eyes, where she was told they could halt or even cure the macular degeneration threatening her sight.
Five days after the injections, the clinic was boasting online that it had performed the first such treatment in Georgia for macular degeneration. On Facebook, the clinic called Tyler “our fabulous patient!” and urged others with her disease to book an appointment.
But by then, Tyler’s vision was getting blurry.
Within weeks, the retina in her left eye detached. Then went the retina in her right eye, according to a lawsuit Tyler and her husband filed in March against the clinic. Surgery after surgery failed to repair the damage. She quickly lost the ability to read large-text print. She could no longer make out the faces of her seven grandchildren.
Within months, she said, she was completely blind.
“We trusted these people. We never questioned that they knew what they were doing,” Tyler said at her Florida home.
The Tylers’ lawsuit alleges negligence by the clinic that treated her, the network to which it belongs and an outside eye doctor. The clinic’s owner and employees and the eye doctor declined to answer repeated calls and emailed questions. The co-founders of the clinic network said neither it nor the Georgia facility did anything wrong.
For years, such direct-to-consumer stem cell clinics have expanded mostly unchallenged. Cases like Tyler’s, however, are prompting lawsuits and new efforts by state and federal regulators to rein in potentially dangerous and worthless treatments.
Last year, California passed a law requiring stem cell clinics to post warnings that their treatments were unapproved, and Washington’s legislature passed a similar law this year. North Dakota’s attorney general is investigating a Bismarck clinic. And the Federation of State Medical Boards is exploring ways to increase oversight of the clinics.
In interviews, Food and Drug Administration Commissioner Scott Gottlieb and his predecessor blamed the agency’s limited resources for the lack of aggressive action in the past. Since last summer, Gottlieb has promised to pursue “unscrupulous actors” who he says are putting the promising field of stem cell therapies at risk.
The agency, which had issued only seven warning letters in seven years to stem cell clinics and suppliers, has sent two such letters since August. It also ordered the seizure of an experimental concoction made of stem cells and given to cancer patients.
Late last year, officials clarified previously murky policies to assert that many of the treatments clinics offer are unapproved drugs, a key point of contention. The facilities argue they aren’t subject to FDA regulation because they use surgical procedures to administer patients’ own cells — meaning they aren’t making new drugs.
But the agency now insists that their therapies require advance approval because the cells are intended to treat diseases and undergo substantial processing before being used in ways that are different from their original purposes.
Acknowledging the difficulty of curbing the entire booming industry, FDA officials say their crackdown will first focus on high-risk procedures such as injections into the brain, spinal cord and eye — rather than less risky ones, such as shots into achy joints.
This month, Sen. Charles E. Grassley (R-Iowa) sent a letter to the FDA, pushing for stronger action. Grassley cited the cases of three women who suffered permanent loss of vision at a Florida facility called U.S. Stem Cell Clinic. He asked what has been done to ensure such dangerous procedures aren’t performed again.
Clinic operators say desperately ill patients have a right to use their own cells for experimental therapies. They say their treatments have the ability to find and repair damaged tissues and organs, and they cite online testimonials from satisfied customers as evidence.
Regulators and researchers disagree, saying strict regulations do apply because the clinics are essentially conducting human experiments without proper oversight.
“What they’re really selling is false hope,” said Timothy Caulfield, a health law professor at the University of Alberta. “It’s science-ploitation. They’re taking a legitimate and developing field of science and using it to prey on patients who are desperate for a cure.”
The treatments are not covered by insurance. Many of the clinics’ patients are old, sick and already struggling with medical bills. Some clinics urge individuals who can’t afford their steep fees — which range from $1,800 to more than $20,000 — to launch GoFundMe pages or take out loans, according to patients and former employees.
Many of the practitioners remain defiant, saying patients need alternative treatments like theirs.
Mark Berman is a Beverly Hills, Calif., plastic surgeon who co-founded Cell Surgical Network, the nation’s largest group of independent stem cell clinics, including the facility that injected material into Tyler’s eyes. After the network learned of her complications, Berman said, it directed all of its affiliated physicians to stop doing such injections into the eye.
Berman said Tyler’s problem was “virtually” the only serious adverse event to occur in his network in treating almost 8,000 patients. But an FDA report in July 2017 listed four adverse cases, including Tyler’s. Berman said the others were “very minor” and called the FDA’s concerns about patient safety “sanctimonious garbage.”
“How do you heal your body? You have to heal yourself,” Berman said. He said it’s “asinine” for the FDA to call patients’ own cells a drug.
For Tyler, however, the debate over the clinics has come too late.
Before the injections, she could still read large-print books and navigate her home in Ocoee. But now she moves cautiously, clutching each piece of furniture like a life raft. Her husband has learned to cook for them both, and Tyler — a former music teacher who is 77 — had to quit her church choir because she can no longer read the music.
“When I wake up in the morning, one of the hardest things is opening my eyes and seeing that everything is still dark,” she said recently. “And it’s going to be this way until I go to sleep.”
Yet what saddens her most, she said, is that she will never see her youngest grandchildren grow up. In her mind’s eye, they are frozen at ages 1 and 3.
Researchers say there is real promise in stem cells’ ability to self-renew and turn into other types of cells. They are methodically developing stem cell therapies for many types of disorders, including macular degeneration, which can destroy the central vision of the eye. British researchers recently said in a peer-reviewed clinical trial report that two patients who were implanted with an engineered stem cell patch to replace failing cells regained some vision.
But bringing such treatments — tested and refined in rigorous trials — safely to market will take years, experts say.
Only a few stem cell therapies have been approved by the FDA, primarily products made from placental and umbilical cord blood and used to treat leukemia and other blood diseases.
No one tracks how many injuries have occurred from unproven, direct-to-consumer treatments. Such cases have become public in recent years only when doctors write about them in medical journals or patients file lawsuits.
Two years ago, the New England Journal of Medicine published an account of a man who ended up with a huge spinal growth after getting fetal stem cell injections overseas. A 69-year-old woman died in 2010 after a doctor at a Florida clinic injected bone marrow stem cells into the arteries of her brain. In 2012, the same doctor infused fat-derived stem cells into the bloodstream of a man who died soon after, according to the findings of a state health department administrative hearing. But it wasn’t until 2013 that Florida’s state medical board revoked that physician’s license.
Financial harm is also a hazard. Some clinics use high-pressure sales tactics more typical of condominium time-shares than of medical procedures — complete with recruitment seminars, on-the-spot discounts and emotional patient-testimonial videos, according to patients and former employees who attended such seminars.
Some clinics list their unapproved, paid procedures as “studies” on ClinicalTrials.gov, a database maintained by the National Institutes of Health. Critics say they are using the database inappropriately to attract clients and give their treatments an air of legitimacy.
Most trials for new experimental therapies, unlike the stem cell clinic procedures, are overseen as part of the FDA’s investigational new-drug program and free for participants. But NIH doesn’t independently verify the information or indicate whether a “trial” listed in the database was reviewed by the FDA. The site recently added more visible disclaimers to warn consumers. Grassley expressed concern in his recent letter to regulators that the database is being misused.
An NIH spokesperson said the agency “does not assess the quality of clinical research studies — that is the role of funders, regulators and ethics review boards, among others.”
“We’re afraid that these charlatans will besmirch the reputation of legitimate work we have spent decades trying to bring to the clinic,” said Charles Murry, director of the Institute for Stem Cell and Regenerative Medicine at the University of Washington.
Patients who say they benefit from treatments at stem cell clinics could be experiencing the placebo effect or some biological improvement, Murry said. For conditions like arthritis, “these cells may be able to talk to our immune system and say, ‘Cool it,’ ” thus providing temporary relief — like a weak steroid shot.
But unless such treatments are tested in rigorous trials, he said, there’s no way to know whether they are safe and effective.
The first stem cell clinics popped up during the early 2000s in countries with lax regulations — like China, Russia and South Korea — and targeted desperate American “medical tourists.” U.S. doctors soon followed. For many, especially plastic surgeons, sucking out patients’ adipose tissue, or fat, was already routine.
Stem cell clinics have exploded in number across the United States. In 2009, there were two; today, there are at least 700 and likely hundreds more, according to Leigh Turner, a University of Minnesota bioethicist, and Paul Knoepfler, a stem cell biologist at the University of California at Davis, who have compiled a database. In the past four years, at least 150 new facilities have opened every year.
The clinic that treated Tyler is in a sleepy suburb 40 minutes outside of Atlanta. It’s part of the Ageless Wellness Center, which business records show was founded in 2008 by Jamie Walraven, a former emergency room physician, and nurse practitioner Linda Faulkner.
For years, the two offered mostly Botox, laser hair removal and other beauty services. In 2014, they added stem cell treatments to their business model.
The Georgia clinic says on its website that adult stem cells derived from fat are capable of fixing various defects and diseases throughout the body. In a promotional video for the clinic, patients say injections reduced their neck and knee pain and multiple sclerosis symptoms.
Many researchers scoff at the idea that adult stem cells can circulate throughout the body correcting almost any problem. “This idea of a magic bullet that can go around and fill in gaps in the body is science fiction,” said Sally Temple, co-founder of the Neural Stem Cell Institute in Rensselaer, N.Y. She said she doubts there are any stem cells in the processed material most clinics inject back into patients.
In a June 2016 advertisement in a local newspaper, Walraven said her clinic had used fat-derived stem cells to treat multiple sclerosis, osteoarthritis, stroke, rheumatoid arthritis and Parkinson’s disease. In coming weeks, she added, “We have an ophthalmologist who is going to treat three people with macular degeneration.”
Tyler was the first of those patients.
In the spring of 2016, as Tyler continued struggling with macular degeneration, a family friend gave her and her husband a book, “The Stem Cell Revolution.” In it, plastic surgeon Berman and his partner, urologist Elliot Lander, recount how they developed their technique partly from doctors in South Korea and Japan. They started treating patients in California and later launched Cell Surgical Network, which now totals more than 100 stem cell clinics nationwide, including the Ageless Wellness Center facility that treated Tyler’s eyes.
For a fee, Berman and Lander teach other doctors how to extract patients’ fat through liposuction and process it using a proprietary centrifuge called the “Time Machine.” The machine and instruction cost about $30,000, they said.
“People license our brand, and what we give them is training and unlimited professional and technical support,” Lander said. He said affiliated clinics are required to provide Cell Surgical Network with the outcomes of their procedures so it can track patients over time.
The two doctors say the FDA, in taking a tougher stand, is acting on behalf of the pharmaceutical industry, which doesn’t want competition for its medicines.
Visitors to the network website who scroll down toward the bottom of its homepage are told that “stem cell treatment is not approved by the FDA for any specific disease.” If they click for details, they are told that the clinics’ therapies are not being offered as “a cure for any condition, disease, or injury.”
But the website lists dozens of diseases, including congestive heart failure, muscular dystrophy and stroke that Cell Surgical Network is “currently studying.” Patients are charged fees for treatments — in what Berman calls “patient-funded research.”
Walraven, at the Georgia clinic, had never treated macular degeneration but seemed eager to try, the Tylers said.
According to the lawsuit the couple filed in a Georgia state court, the clinic said the treatment would improve Doris Tyler’s vision or, at worst, have no effect.
To raise the $8,900 fee for her procedure, the Tylers’ son set up a GoFundMe account that got an enthusiastic response. “We love you, Doris!” one person wrote on the site. “If you need extra belly fat, I’m MORE than happy to offer mine!” another said.
Walraven asked Robert Halpern, an Atlanta ophthalmologist, to perform the injections. In a June 30, 2016, letter that Tyler’s lawyer shared with The Washington Post, Walraven sent Halpern a brochure explaining how he could become a certified doctor within the network.
Halpern injected Tyler’s right eye on Sept. 8, 2016. The next day he injected her left eye, the lawsuit alleges. Injecting both eyes so close together is a safety risk, eye experts say, because if something goes wrong, patients can be left entirely blind.
Thomas Albini, an ophthalmologist at the University of Miami’s Bascom Palmer Eye Institute, treated Tyler after the stem cell procedure but could not reverse the damage. Albini, retained as an expert witness in the Tylers’ lawsuit, said he believes the processed fat that was injected into Tyler’s eyes may have contained fibroblasts — connective tissue cells that can cause scarring and “literally pull the retinas off the wall of the eye,” in a process called proliferative vitreoretinopathy.
The Georgia clinic, Walraven, Faulkner and Halpern declined to answer repeated calls and emailed questions. None has responded in court to the allegations.
Lander said all clinics in Cell Surgical Network use a “very, very thorough” consent form that spells out all the risks, such as, in Tyler’s case, her vision potentially getting worse.
The Tylers’ lawyer, Andrew Yaffa, said that was a “misrepresentation.” He said she was given one consent form that said she would be participating in what was described as a research study. Other forms warned of possible complications from the injections, Yaffa said, but not from the stem cells themselves.
Yaffa represented two women who reached confidential settlements after losing vision following stem cell injections for macular degeneration at U.S. Stem Cell Clinic in southern Florida — among the cases detailed in a New England Journal of Medicine article last year.
Berman said the Georgia clinic that treated Tyler “did everything right,” noting that a retina specialist performed the injections and that Cell Surgical Network halted such eye injections as soon as he and Lander heard about Tyler’s complications.
But Ajay Kuriyan, a retinal specialist at the University of Rochester, said he and other researchers have found dozens of clinics that continue to market such eye injections on their websites. After writing that 2017 article on the three women who suffered severe eye damage at the Florida facility, Kuriyan said he and his co-authors received a flurry of calls about other cases.
“The problem is still there,” he said.
In August, the FDA sent a warning letter to U.S. Stem Cell Clinic; in January, another warning letter went to American CryoStem Corp. in New Jersey, which processes and distributes a fat-derived stem cell product. Both companies, the agency said, were selling unapproved drugs — in the case of U.S. Stem Cell Clinic, for heart disease, amyotrophic lateral sclerosis and diabetes, among other diseases — and deviating from proper manufacturing practices.
In response, CryoStem said it would “actively engage with the agency to resolve these issues and continue to improve our quality systems and processes.”
U.S. Stem Cell Clinic told the FDA that it isn’t making a drug and isn’t subject to agency regulation, and it asserted that patients have a right to alternative treatments. It denied having sterility problems in its operation. In an interview, Chief Science Officer Kristin Comella said the clinic no longer does eye injections and “the cases have been settled.”
Her goal, she added, is “to always help people achieve health and help them feel good, and when they don’t, it’s personally devastating.”
The company continues to expand. It recently opened another facility at a seniors community in central Florida, and it announced plans to inject stem cell mixtures into patients’ penises to treat erectile dysfunction — a $4 billion market, a company release noted.
The FDA last summer also had U.S. marshals seize live vaccinia virus vaccine, used to protect people at risk of smallpox, that was discovered during an agency inspection of a San Diego biotech company named StemImmune. The vaccine, combined with stem cells, was being injected directly into tumors of terminally ill cancer patients and administered intravenously at Lander’s and Berman’s two California clinics, the agency said. The FDA said the vaccine posed “substantial risks,” including myocarditis, an inflammation of the heart muscle.
Allan Camaisa, chief executive of StemImmune, said the company is “cooperating fully” and will continue talking to officials about cancer treatments. Berman said the FDA misrepresented what the clinics were doing.
In recent months, the FDA has stepped up its oversight efforts. It spelled out procedures designed to speed approval of legitimate stem cell therapies. It also detailed under what circumstances direct-to-consumer stem cell treatments require agency approval.
Of the decision to focus its enforcement on “high-risk” procedures, Gottlieb said there’s only so much that can be done: “You can’t boil the ocean.”
Many researchers say the moves fall short. Temple, the stem cell scientist, is blunt: “I’d like the FDA to be firmly shutting all these places down.”