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PLoS Med. 2009 Feb 17;6(2):e1000029. doi: 10.1371/journal.pmed.1000029.

Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient.

Author information

1
Cancer Research Center, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel.

Abstract

BACKGROUND:

Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells.

METHODS AND FINDINGS:

A boy with ataxia telangiectasia (AT) was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA) typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors.

CONCLUSIONS:

This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.

PMID:
19226183
PMCID:
PMC2642879
DOI:
10.1371/journal.pmed.1000029
[Indexed for MEDLINE]
Free PMC Article

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