Friday, July 1, 2016

Stem cell tourism

A new case report describes a patient who developed a glioproliferative neoplasm of the spinal cord after stem cell transplants at commercial clinics in China, Argentina, and Mexico.

The 66-year-old man was seeking to ease residual deficits from ischemic stroke when he visited these clinics, where he underwent intrathecal infusions of mesenchymal, embryonic, and fetal neural stem cells, according to clinic reports.

He wasn't given any immunosuppressive drugs and subsequently developed the glioproliferative neoplasm.

This case highlights the risks of "stem-cell tourism," say the authors of a letter to the editor describing the case, published online June 22 in The New England Journal of Medicine.

Commercial stem-cell clinics now operate worldwide with limited or no regulation, Aaron L. Berkowitz, MD, PhD, and colleagues from Brigham and Women's Hospital, Boston, Massachusetts, point out in their letter.

After his stem cell treatments, the patient experienced progressive lower back pain, paraplegia, and urinary incontinence. MRI revealed a lesion of the thoracic spinal cord and thecal sac, and a biopsy specimen was obtained.

Neuropathologic analysis showed a densely cellular, highly proliferative, primitive neoplasm with glial differentiation. "Short tandem repeat DNA fingerprinting analysis indicated that the mass was predominantly composed of nonhost cells," the authors say.

On the basis of histopathologic and molecular studies, the glioproliferative lesion appeared to have originated from the intrathecally introduced exogenous stem cells.
"The lesion had some features that overlapped with malignant gliomas (nuclear atypia, a high proliferation index, glial differentiation, and vascular proliferation) but did not show other features typical of cancer (no cancer-associated genetic aberrations were detected on next-generation sequencing of 309 cancer-associated genes)," they note.

So while the lesion may be a considered a neoplasm, it didn't fit in any category of previously described human neoplasm on the basis of the data they had, Dr Berkowitz and colleagues say.

The patient underwent radiation therapy, which led to a decrease in back pain, improved mobility of the right leg, and decreased the bulk of the lesion on MRI.

"Embryonic and other stem cells have tumorigenic potential and have been proposed as a source of common origin for cancer," the authors note. This case and others in which tumors have developed in the context of stem-cell tourism illustrate "an extremely serious complication of introducing proliferating stem cells into patients," they caution.

"The unregulated commercial stem-cell industry is not only potentially harmful to individual patients," they conclude, "but also undermines attempts to study stem-cell therapies in clinical trials.

They say this case further supports the conclusions of a recent article calling for increased investigation of commercial stem-cell clinics and increased patient education regarding the risks of stem-cell tourism. "Such experimental treatments must be studied in a safe, regulated environment," Dr Berkowitz and colleagues conclude.

Berkowitz AL, Miller MB, Mir SA, Cagney D, Chavakula V, Guleria I, Aizer A, Ligon KL, Chi JH. Glioproliferative Lesion of the Spinal Cord as a Complication of "Stem-Cell Tourism". N Engl J Med. 2016 Jun 22. [Epub ahead of print]


  1. While the case report did not identify the patient, the man disclosed his identity to the media. In an interview with the New York Times, Jim Gass of San Diego, said he searched the Internet and spent close to $300,000 for treatments and travel costs in the hopes of reversing lingering damage from a 2009 stroke. The article said the spine tumor left him far worse off — “paralyzed from the neck down, except for his right arm,” and the tumor is still growing.

    The doctors described the case as “stem cell tourism” gone awry.

    “This case and others in which tumors have developed in the context of stem-cell tourism...illustrate an extremely serious complication of introducing proliferating stem cells into patients,” they wrote. They noted, in contrast, that stem cell researchers working on new therapies utilize techniques that “reduce the risk of stem-cell-related tumors in clinical trials by means of the measured administration of pluripotent stem cells or by differentiating stem cells in vitro into postmitotic phenotypes before administration.”

    “The unregulated commercial stem-cell industry is not only potentially harmful to individuals, but also undermines attempts to study stem-cell therapies in clinical trials,” the doctors noted...

    While the man in the case report sought out treatment in other countries, there are many commercial stem cell clinics popping up around the United States. A study in the June 30 online edition of Cell Stem Cell found that there are 571 so-called stem cell clinics operated by 351 businesses around the country. [Neurology Today reported on unregulated stem cell clinics in the US last year. See “Unregulated Stem Cell Clinics Proliferate in the US, Despite 2013 Court Ruling”:]Such clinics in the US and abroad advertise treatments for everything from achy joints to sagging faces to neurologic conditions such as Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Parkinson's disease...

    “Stem cells have the characteristic ability to self-renew or replicate,” meaning it is possible that a tumor could arise from the proliferating cells. These are potentially dangerous cells to administer to the patient, especially in the central nervous system,” he said.Clive Svendsen, PhD, a stem cell researcher at Cedars-Sinai David Geffen School of Medicine at the University of California, Los Angeles, said the case illustrates the serious unintended consequences that can occur when investigational therapies are administered outside the safety net of government regulations and peer review. Besides such tumors, there could be infection or a dangerous immune response.

  2. Turner L, Knoepfler P. Selling Stem Cells in the USA: Assessing the
    Direct-to-Consumer Industry. Cell Stem Cell. 2016 Jun 29.

    Direct-to-consumer marketing of unapproved stem cell interventions is a well-known phenomenon in countries with lax medical regulations. However, an examination of Internet-based marketing claims revealed widespread promotion of such interventions by businesses based in the United States. Such commercial activity suggests that regulatory agencies must better oversee this marketplace.

    Turner L. US stem cell clinics, patient safety, and the FDA. Trends Mol Med. 2015 May;21(5):271-3.

    Scholarship on patients accessing unproven stem cell interventions is dominated by research addressing 'stem cell tourism' to such countries as China, India, Mexico, and the Ukraine. However, clinics marketing 'adipose-derived mesenchymal stem cell treatments' are proliferating across the USA. These businesses typically claim to operate in compliance with federal regulations, but careful review of their commercial practices suggests that such clinics are marketing unapproved and noncompliant biological drugs.