Differential Secondary Reconstitution of In Vivo-Selected Human SCID-Repopulating Cells in NOD/SCID versus NOD/SCID/gamma chain(null) Mice

被引：13

作者：

Cai, Shanbao ^{[1
,2
]}

Wang, Haiyan ^{[1
,2
]}

Bailey, Barbara ^{[1
,3
]}

Hartwell, Jennifer R. ^{[1
,2
]}

Silver, Jayne M. ^{[3
]}

Juliar, Beth E. ^{[4
]}

Sinn, Anthony L. ^{[3
]}

Baluyut, Arthur R. ^{[5
]}

Pollok, Karen E. ^{[1
,3
]}

机构：

[1] Indiana Univ Simon Canc Ctr, Riley Hosp Children, Sect Pediat Hematol Oncol, Dept Pediat, 980 WestWalnut St R3516, Indianapolis, IN 46202 USA

[2] Indiana Univ Simon Canc Ctr IUSCC, Indiana Univ Sch Med IUSM, Indianapolis, IN 46202 USA

[3] IUSCC, Vivo Therapeut Core, Indianapolis, IN 46202 USA

[4] IUSCC, Biostatist & Data Management Core, Indianapolis, IN 46202 USA

[5] St Vincent Hosp, Northside Gastroenterol, Indianapolis, IN 46260 USA

来源：

BONE MARROW RESEARCH | 2011年

关键词：

D O I：

10.1155/2011/252953

中图分类号：

R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学（修复外科学）];

学科分类号：

摘要：

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/gamma 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/gamma chain(null) mice compared to NOD/SCID mice at 2 months after transplantation. These data indicate that reconstitution of NOD/SCID/gamma 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.

引用

页数：11

共 49 条

[1] Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning [J].