Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient
Ninette Amariglio1,2, Abraham Hirshberg3, Bernd W. Scheithauer4, Yoram Cohen1, Ron Loewenthal5, Luba Trakhtenbrot2, Nurit Paz1, Maya Koren-Michowitz2, Dalia Waldman6, Leonor Leider-Trejo7, Amos Toren6, Shlomi Constantini8, Gideon Rechavi1,6*
1 Cancer Research Center, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel, 2 Institute of Hematology, Sheba Medical Center, Tel Hashomer, Israel, 3 Department of Oral Pathology, School of Dental Medicine, Tel Aviv University, Tel-Aviv, Israel, 4 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America, 5 Tissue Typing Laboratory, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel, 6 Department of Pediatric Hemato-Oncology, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel, 7 Institute of Pathology, Tel-Aviv Medical Center, Tel-Aviv, Israel, 8 Pediatric Neurosurgery, Dana Children''s Hospital, Tel-Aviv Medical Center, and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel
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.
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.
Citation: Amariglio N, Hirshberg A, Scheithauer BW, Cohen Y, Loewenthal R, et al. (2009) Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient. PLoS Med 6(2): e1000029. doi:10.1371/journal.pmed.1000029
Academic Editor: Alain Fischer, Hôpital Necker-Enfants Malades, France
Received: July 17, 2007; Accepted: December 24, 2008; Published: February 17, 2009
Copyright: © 2009 Amariglio et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors received no specific funding for this study.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: AT, ataxia telangiectasia; BS, buccal smear; ESC, embryonic stem cell; HLA, human leukocyte antigen; I-FISH, interphase fluorescence in situ hybridization; LCM, laser capture microdissection; PB, peripheral blood
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