In:
Bone Marrow Research, Hindawi Limited, Vol. 2011 ( 2011-12-26), p. 1-11
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 chain null mice to support long-term engraftment of MGMT P140K -transduced human-hematopoietic cells following alkylator-mediated in vivo selection was investigated. Mice were transplanted with MGMT P140K -transduced CD34 + cells and transduced cells selected in vivo . At 4 months after transplantation, levels of human-cell engraftment, and MGMT P140K -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 MGMT P140K -transduced human cells were transplanted, engraftment was significantly higher in NOD/SCID/ γ chain null mice compared to NOD/SCID mice at 2 months after transplantation. These data indicate that reconstitution of NOD/SCID/ γ chain null 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.
Type of Medium:
Online Resource
ISSN:
2090-2999
,
2090-3006
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2011
detail.hit.zdb_id:
2623734-9
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