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

Author:

Cai Shanbao12,Wang Haiyan12,Bailey Barbara13,Hartwell Jennifer R.12,Silver Jayne M.3,Juliar Beth E.4,Sinn Anthony L.3,Baluyut Arthur R.5,Pollok Karen E.13

Affiliation:

1. 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

2. Indiana University Simon Cancer Center (IUSCC), Indiana University School of Medicine (IUSM), Indianapolis, IN 46202, USA

3. In Vivo Therapeutics Core, IUSCC, Indianapolis, IN 46202, USA

4. Biostatistics and Data Management Core, IUSCC, Indianapolis, IN 46202, USA

5. Northside Gastroenterology, St. Vincent Hospital, Indianapolis, IN 46260, USA

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.

Publisher

Hindawi Limited

Subject

Cell Biology,Hematology,Immunology

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