Nonirradiated NOD,B6.SCID Il2rγ−/− KitW41/W41 (NBSGW) Mice Support Multilineage Engraftment of Human Hematopoietic Cells

In this study, we demonstrate a newly derived mouse model that supports engraftment of human hematopoietic stem cells (HSCs) in the absence of irradiation. We cross the NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) strain with the C57BL/6J-KitW-41J/J (C57BL/6.KitW41) strain and engraft, without irradiation,...

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Main Authors: Brian E. McIntosh, Matthew E. Brown, Bret M. Duffin, John P. Maufort, David T. Vereide, Igor I. Slukvin, James A. Thomson
Format: Article
Language:English
Published: Elsevier 2015-02-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671114003828
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author Brian E. McIntosh
Matthew E. Brown
Bret M. Duffin
John P. Maufort
David T. Vereide
Igor I. Slukvin
James A. Thomson
author_facet Brian E. McIntosh
Matthew E. Brown
Bret M. Duffin
John P. Maufort
David T. Vereide
Igor I. Slukvin
James A. Thomson
author_sort Brian E. McIntosh
collection DOAJ
description In this study, we demonstrate a newly derived mouse model that supports engraftment of human hematopoietic stem cells (HSCs) in the absence of irradiation. We cross the NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) strain with the C57BL/6J-KitW-41J/J (C57BL/6.KitW41) strain and engraft, without irradiation, the resulting NBSGW strain with human cord blood CD34+ cells. At 12-weeks postengraftment in NBSGW mice, we observe human cell chimerism in marrow (97% ± 0.4%), peripheral blood (61% ± 2%), and spleen (94% ± 2%) at levels observed with irradiation in NSG mice. We also detected a significant number of glycophorin-A-positive expressing cells in the developing NBSGW marrow. Further, the observed levels of human hematopoietic chimerism mimic those reported for both irradiated NSG and NSG-transgenic strains. This mouse model permits HSC engraftment while avoiding the complicating hematopoietic, gastrointestinal, and neurological side effects associated with irradiation and allows investigators without access to radiation to pursue engraftment studies with human HSCs.
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spelling doaj.art-2d630842a39c43368e62ccb99ba8c2eb2022-12-21T19:02:44ZengElsevierStem Cell Reports2213-67112015-02-014217118010.1016/j.stemcr.2014.12.005Nonirradiated NOD,B6.SCID Il2rγ−/− KitW41/W41 (NBSGW) Mice Support Multilineage Engraftment of Human Hematopoietic CellsBrian E. McIntosh0Matthew E. Brown1Bret M. Duffin2John P. Maufort3David T. Vereide4Igor I. Slukvin5James A. Thomson6Morgridge Institute for Research, Madison, WI 53715, USADepartment of Surgery, University of Wisconsin, Madison, WI 53715, USAMorgridge Institute for Research, Madison, WI 53715, USAMorgridge Institute for Research, Madison, WI 53715, USAMorgridge Institute for Research, Madison, WI 53715, USAWisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USAMorgridge Institute for Research, Madison, WI 53715, USAIn this study, we demonstrate a newly derived mouse model that supports engraftment of human hematopoietic stem cells (HSCs) in the absence of irradiation. We cross the NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) strain with the C57BL/6J-KitW-41J/J (C57BL/6.KitW41) strain and engraft, without irradiation, the resulting NBSGW strain with human cord blood CD34+ cells. At 12-weeks postengraftment in NBSGW mice, we observe human cell chimerism in marrow (97% ± 0.4%), peripheral blood (61% ± 2%), and spleen (94% ± 2%) at levels observed with irradiation in NSG mice. We also detected a significant number of glycophorin-A-positive expressing cells in the developing NBSGW marrow. Further, the observed levels of human hematopoietic chimerism mimic those reported for both irradiated NSG and NSG-transgenic strains. This mouse model permits HSC engraftment while avoiding the complicating hematopoietic, gastrointestinal, and neurological side effects associated with irradiation and allows investigators without access to radiation to pursue engraftment studies with human HSCs.http://www.sciencedirect.com/science/article/pii/S2213671114003828
spellingShingle Brian E. McIntosh
Matthew E. Brown
Bret M. Duffin
John P. Maufort
David T. Vereide
Igor I. Slukvin
James A. Thomson
Nonirradiated NOD,B6.SCID Il2rγ−/− KitW41/W41 (NBSGW) Mice Support Multilineage Engraftment of Human Hematopoietic Cells
Stem Cell Reports
title Nonirradiated NOD,B6.SCID Il2rγ−/− KitW41/W41 (NBSGW) Mice Support Multilineage Engraftment of Human Hematopoietic Cells
title_full Nonirradiated NOD,B6.SCID Il2rγ−/− KitW41/W41 (NBSGW) Mice Support Multilineage Engraftment of Human Hematopoietic Cells
title_fullStr Nonirradiated NOD,B6.SCID Il2rγ−/− KitW41/W41 (NBSGW) Mice Support Multilineage Engraftment of Human Hematopoietic Cells
title_full_unstemmed Nonirradiated NOD,B6.SCID Il2rγ−/− KitW41/W41 (NBSGW) Mice Support Multilineage Engraftment of Human Hematopoietic Cells
title_short Nonirradiated NOD,B6.SCID Il2rγ−/− KitW41/W41 (NBSGW) Mice Support Multilineage Engraftment of Human Hematopoietic Cells
title_sort nonirradiated nod b6 scid il2rγ kitw41 w41 nbsgw mice support multilineage engraftment of human hematopoietic cells
url http://www.sciencedirect.com/science/article/pii/S2213671114003828
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