PMID- 19226183
OWN - NLM
STAT- MEDLINE
DCOM- 20090429
LR  - 20220408
IS  - 1549-1676 (Electronic)
IS  - 1549-1277 (Print)
IS  - 1549-1277 (Linking)
VI  - 6
IP  - 2
DP  - 2009 Feb 17
TI  - Donor-derived brain tumor following neural stem cell transplantation in an ataxia 
      telangiectasia patient.
PG  - e1000029
LID - 10.1371/journal.pmed.1000029 [doi]
LID - e1000029
AB  - 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.
FAU - Amariglio, Ninette
AU  - Amariglio N
AD  - Cancer Research Center, Sheba Medical Center and Sackler School of Medicine, Tel 
      Aviv University, Tel-Aviv, Israel.
FAU - Hirshberg, Abraham
AU  - Hirshberg A
FAU - Scheithauer, Bernd W
AU  - Scheithauer BW
FAU - Cohen, Yoram
AU  - Cohen Y
FAU - Loewenthal, Ron
AU  - Loewenthal R
FAU - Trakhtenbrot, Luba
AU  - Trakhtenbrot L
FAU - Paz, Nurit
AU  - Paz N
FAU - Koren-Michowitz, Maya
AU  - Koren-Michowitz M
FAU - Waldman, Dalia
AU  - Waldman D
FAU - Leider-Trejo, Leonor
AU  - Leider-Trejo L
FAU - Toren, Amos
AU  - Toren A
FAU - Constantini, Shlomi
AU  - Constantini S
FAU - Rechavi, Gideon
AU  - Rechavi G
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - PLoS Med
JT  - PLoS medicine
JID - 101231360
SB  - IM
MH  - Adolescent
MH  - Ataxia Telangiectasia/*surgery
MH  - Brain Neoplasms/diagnosis/*etiology/*pathology
MH  - Humans
MH  - Living Donors
MH  - Male
MH  - Neurons/*pathology/*transplantation
MH  - Stem Cell Transplantation/*adverse effects
MH  - Stem Cells/*pathology
PMC - PMC2642879
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/02/20 09:00
MHDA- 2009/04/30 09:00
PMCR- 2009/02/17
CRDT- 2009/02/20 09:00
PHST- 2007/07/17 00:00 [received]
PHST- 2008/12/24 00:00 [accepted]
PHST- 2009/02/20 09:00 [entrez]
PHST- 2009/02/20 09:00 [pubmed]
PHST- 2009/04/30 09:00 [medline]
PHST- 2009/02/17 00:00 [pmc-release]
AID - 07-PLME-RA-1020 [pii]
AID - 07-PLME-RA-1020R3 [pii]
AID - 10.1371/journal.pmed.1000029 [doi]
PST - ppublish
SO  - PLoS Med. 2009 Feb 17;6(2):e1000029. doi: 10.1371/journal.pmed.1000029.