Back to Search Start Over

Differential Secondary Reconstitution of In Vivo-Selected Human SCID-Repopulating Cells in NOD/SCID versus NOD/SCID/γ chain Mice

Authors :
Anthony L. Sinn
Jayne M. Silver
Karen E. Pollok
Haiyan Wang
Barbara J. Bailey
Beth E. Juliar
Jennifer R. Hartwell
Shanbao Cai
Arthur R. Baluyut
Source :
Bone Marrow Research, Bone Marrow Research, Vol 2011 (2011)
Publication Year :
2010

Abstract

Humanized bone-marrow xenograft models that can monitor the long-term impact of gene-therapy strategies will help facilitate evaluation of clinical utility. The ability of the murine bone-marrow microenvironment in NOD/SCID versus NOD/SCID/γ chainnull mice to support long-term engraftment of MGMTP140K-transduced human-hematopoietic cells following alkylator-mediated in vivo selection was investigated. Mice were transplanted with MGMTP140K-transduced CD34+ cells and transduced cells selected in vivo. At 4 months after transplantation, levels of human-cell engraftment, and MGMTP140K-transduced cells in the bone marrow of NOD/SCID versus NSG mice varied slightly in vehicle- and drug-treated mice. In secondary transplants, although equal numbers of MGMTP140K-transduced human cells were transplanted, engraftment was significantly higher in NOD/SCID/γ chainnull mice compared to NOD/SCID mice at 2 months after transplantation. These data indicate that reconstitution of NOD/SCID/γ chainnull mice with human-hematopoietic cells represents a more promising model in which to test for genotoxicity and efficacy of strategies that focus on manipulation of long-term repopulating cells of human origin.

Details

ISSN :
20903006
Volume :
2011
Database :
OpenAIRE
Journal :
Bone marrow research
Accession number :
edsair.doi.dedup.....4ce69442033a06286c35fc800f0efae0