title: Differential Secondary Reconstitution of In Vivo-Selected Human SCID-Repopulating Cells in NOD/SCID versus NOD/SCID/γ chain Mice.
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.
authors: Section of Pediatric Hematology/Oncology, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University Simon Cancer Center, The Riley Hospital for Children, 980 West Walnut Street, R3 516, Indianapolis, IN 46202-5525, USA.
authors: Shanbao
authors: S
authors: Cai
authors: Haiyan
authors: H
authors: Wang
authors: Barbara
authors: B
authors: Bailey
authors: Jennifer R
authors: JR
authors: Hartwell
authors: Jayne M
authors: JM
authors: Silver
authors: Beth E
authors: BE
authors: Juliar
authors: Anthony L
authors: AL
authors: Sinn
authors: Arthur R
authors: AR
authors: Baluyut
authors: Karen E
authors: KE
authors: Pollok