Monday, July 1, 2019

Stem cell therapy


Last year, a 77-year-old woman traveled to a clinic in Georgia to have stem cells injected in her eyes. She came in hope of a cure—or at least something that could help her macular degeneration, which causes a dark spot to appear in the center of vision.

The procedure was supposed to work like this: The clinic would take fat from her belly, separate out stem cells that naturally occur in fat, and inject them into her eyes to regenerate damaged tissue. The procedure cost $8,900. It had not been approved by the Food and Drug Administration and was not covered by insurance. To pay out of pocket, she had to raise money on a crowdfunding site. 

Her vision did not get better. It got much worse. Within three months, her retinas—the eye’s layer of light-sensitive cells—had peeled away from the rest of her eyes. As a result, she can only make out hand motions in her right eye and light in the left, according to a recent case report. She could no longer walk on her own.

In March, eye doctors based primarily at the Bascom Palmer Eye Institute in Miami had published a widely covered report describing three eerily similar cases: Three elderly women with macular degeneration got stem cells derived from their own fat injected into their eyes at a different stem-cell clinic in Florida. The same thing happened: Their retinas became detached, and they went blind. The doctors ended up examining the 77-year-old woman too, which led to the recent case report describing her condition.

And there are likely even more cases. Since writing the first report, says Ajay Kuriyan, an author on the report and now a retinal specialist at the University of Rochester, eye doctors around the country have come forward with similar stories of stem-cell injections gone awry. They are now preparing an article describing the additional cases.

Stem-cell clinics that offer seeming miracle cures for everything from back pain to erectile dysfunction have proliferated in the United States in the past decade. These cases of blindness now cropping up in the medical literature point to the potential dangers of letting hundreds of such clinics operate without oversight.

In August, the FDA moved toward a crackdown. It posted a warning letter to the Florida clinic that had treated the first three women and called the fat-derived stem cells an unapproved treatment. On the same day, the agency announced that federal marshals had seized live-virus vaccines from a California company that was injecting the viruses along with stem cells into cancer patients. After the news broke, says Mark Berman, a plastic surgeon and the California company’s director of stem-cell implantation,“I’ve actually had patients call me up, cancel their surgery, demand their money back, and tell me what a disgusting human being I am and I should be removed from this planet.” He criticized the initial news reports as “classic leftist kind of propaganda, fake news.”

Berman also cofounded the Cell Surgical Network, of which the Georgia clinic that treated the 77-year-old woman is an affiliate. The network trains affiliated doctors to use their equipment and follow their stem-cell therapy protocols.

The case report does not name the Georgia clinic, but The Atlantic has independently confirmed it is the Stem Cell Center of Georgia, which operates within the Ageless Wellness Center in Peachtree City. The clinic declined to comment for this story. A local news report from June 2016 quotes the center’s doctor as saying, “We have an ophthalmologist who is going to treat three people with macular degeneration with intraocular injections.”

Berman says that his network’s affiliates have performed about 15 eye procedures total. They stopped offering it after the woman went blind. (Cell Surgical Network and the Stem Cell Center of Georgia both still list macular degeneration on their websites.) The injections, he says, were part of a study approved by an institutional review board. At the clinic, the 77-year-old woman received injections into her two eyes one day apart. Berman concedes that they should have waited longer to make sure there were no serious side effects after the first eye. “That’s a pretty good lesson learned. Unfortunately it was learned by doing them,” he says.

Others say the clinic should have known better. “It’s just not a professional thing to take an unproven intervention and inject it in both eyes,” says Leigh Turner, a bioethicist at the University of Minnesota, who tracks stem-cell clinics. Kuriyan says that injecting both eyes and asking patients to pay out of pocket for their treatment are both highly unusual for clinical trials. “Those are all big red flags,” he says. A better approach, he says, would have been to test the injections in animals for safety first.

It’s unclear exactly why the stem-cell injections caused such a bad reaction in these women. Perhaps the stem cells had differentiated into cells that formed a membrane and then contracted, peeling the retina away from the rest of the eye. Or perhaps there was scarring caused by immune cells, which are part of the mix of cells in fat that can be injected along with stem cells into the eye.

Given the growing number of retinal detachments coming to light, Turner wonders if there are other consequences of stem-cell injections that have not been reported. Berman says that the Cell Surgical Network has performed 7,000 stem-cell injections into various parts of the body, and the 77-year-old woman’s case is “the only real significant problem we’ve had.” A FDA inspection report from July chastised his network for failing to investigate and report four “serious adverse events” to the FDA, including the 77-year-old woman’s case as well as a hip infection, another “severe infection,” and a case where a patient was hospitalized for confusion and headache.

The FDA has drafted guidelines on how to oversee stem-cell clinics. The agency says stem cells do not have to be regulated as drugs as long as clinics follow certain standards, like if they only minimally manipulate the cells and don’t change their purpose in the body. For example, transferring fat from the belly to breasts would not fall under FDA purview because the fat is still acting as fat. But if stem cells are being separated from fat and then injected to treat a disease, then the FDA may have reason to step in.

“The question to me is, ‘Will the FDA really dedicate the resources that are needed?’” says Turner. The FDA very publicly criticized a couple stem-cell clinics in August as a warning shot, but there are hundreds of such clinics in the United States, and overseeing them all would require a significant investment. In just the five years Turner has been closely tracking the stem-cell industry, he says, business seems to have been booming.


Courtesy of a colleague

Nirwan RS, Albini TA, Sridhar J, Flynn HW Jr, Kuriyan AE. Assessing "Cell Therapy" Clinics Offering Treatments of Ocular Conditions using Direct-to-Consumer Marketing Websites in the United States. Ophthalmology. 2019 Mar 21. pii: S0161-6420(18)32630-7. doi: 10.1016/j.ophtha.2019.03.019. [Epub ahead of print]

Abstract

PURPOSE:
"Cell therapy" is becoming increasingly available to the public via online direct-to-consumer advertisement within the United States (U.S.). The current study investigates the scope of "cell therapy" clinics across the U.S. that advertise and offer "cell therapy" for ocular conditions based on information provided on their websites.

DESIGN:
Cross-sectional study.

PARTICIPANTS:
The study included companies that are U.S.-based, participate in direct-to-consumer online marketing, have websites that can be data-mined with content analysis, and advertise therapy for ocular conditions.

METHODS:
Using a systematic, extensive keyword-based Internet search, content analysis of company websites was utilized to identify, document, and analyze U.S. businesses marketing "cell therapy" for ocular conditions as of September 16, 2017.

MAIN OUTCOME MEASURES:
Clinic locations, source of stem cells used, route of administration, marketed ocular conditions, and cost of treatment.

RESULTS:
Forty companies with 76 clinics use "cell therapy" to treat ocular conditions. California (23), Florida (12), and Illinois (10) contain the most clinics. All 40 companies specified sources of cells, which included autologous adipose-derived stem cells (35; 67%), autologous bone marrow-derived stem cells (8; 15%), amniotic stem cells (2; 4%), peripheral blood-derived stem cells (2; 4%), umbilical cord blood stem cells (2; 4%), allogenic bone marrow-derived stem cells (1; 2%), placental stem cells (1; 2%), and xenocells (1; 2%). The most commonly marketed ocular conditions included macular degeneration (35), optic neuritis (18), retinitis pigmentosa (17), and diabetic retinopathy (16). The most common routes of administration were intravenous (22) and "unspecified" (12); however, other companies listed more ocular-specific routes such as intravitreal injections (2), retrobulbar injections (2), eye injections (2), retrofundal injection (1), sub-Tenon injection (1), intraocular injection with vitrectomy (1), and eye drops (1). The cost of advertised "cell therapy" ranged from $4000 to $10 500.

CONCLUSIONS:
"Cell therapy" for ocular conditions is readily available via direct-to-consumer marketing strategies across the United States. The "cells" are harvested from numerous sources and administered through different methods for multiple ocular conditions at these "cell therapy" clinics. Limited data for these treatments necessitates advocating caution to physicians and patients about treatments offered at commercial "cell therapy" clinics.

Hussain RM, Dubovy SR, Kuriyan AE, Zhou XY, Flynn HW Jr, Albini TA. Clinicopathologic Correlations of Retinal Membranes Associated With Intravitreal 'Stem Cell' Injections. Ophthalmic Surg Lasers Imaging Retina. 2019 Feb 1;50(2):125-131.

Abstract

The histologic findings of a subretinal band and epiretinal membrane (ERM) excised from two patients who developed retinal detachments (RDs) after non-U.S. Food and Drug Administration-regulated intravitreal "stem cell" injections are reported. Both membranes were composed of fibrocellular tissue that stained positively with Smooth Muscle Actin and Masson's trichrome, consistent with collagenous and smooth muscle composition. CD34 immunostain (for hematopoietic cells) was negative for the subretinal band and minimally positive for the ERM. The authors speculate that the "stem cells" may cause RDs by differentiation into myofibroblasts that cause tractional membranes, though further studies are warranted.

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