Document Detail


Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2rγ null mice is enhanced by transgenic expression of membrane-bound human SCF.
MedLine Citation:
PMID:  22246028     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Immunodeficient mice engrafted with human HSCs support multidisciplinary translational experimentation, including the study of human hematopoiesis. Heightened levels of human HSC engraftment are observed in immunodeficient mice expressing mutations in the IL2-receptor common γ chain (IL2rg) gene, including NOD-scid IL2rγ(null) (NSG) mice. Engraftment of human HSC requires preconditioning of immunodeficient recipients, usually with irradiation. Such preconditioning increases the expression of stem cell factor (SCF), which is critical for HSC engraftment, proliferation, and survival. We hypothesized that transgenic expression of human membrane-bound stem cell factor Tg(hu-mSCF)] would increase levels of human HSC engraftment in nonirradiated NSG mice and eliminate complications associated with irradiation. Surprisingly, detectable levels of human CD45(+) cell chimerism were observed after transplantation of cord blood-derived human HSCs into nonirradiated adult as well as newborn NSG mice. However, transgenic expression of human mSCF enabled heightened levels of human hematopoietic cell chimerism in the absence of irradiation. Moreover, nonirradiated NSG-Tg(hu-mSCF) mice engrafted as newborns with human HSCs rejected human skin grafts from a histoincompatible donor, indicating the development of a functional human immune system. These data provide a new immunodeficient mouse model that does not require irradiation preconditioning for human HSC engraftment and immune system development.
Authors:
Michael A Brehm; Waldemar J Racki; Jean Leif; Lisa Burzenski; Vishnu Hosur; Amber Wetmore; Bruce Gott; Mary Herlihy; Ronald Ignotz; Raymond Dunn; Leonard D Shultz; Dale L Greiner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-01-12
Journal Detail:
Title:  Blood     Volume:  119     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-23     Completed Date:  2012-05-07     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2778-88     Citation Subset:  AIM; IM    
Affiliation:
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. michael.brehm@umassmed.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Cell Differentiation / physiology*
Cell Separation
Flow Cytometry
Hematopoietic Stem Cells / cytology*
Humans
Mice
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic*
Stem Cell Factor / genetics,  metabolism*
Transplantation Chimera / physiology*
Transplantation Tolerance / physiology
Grant Support
ID/Acronym/Agency:
AI050864/AI/NIAID NIH HHS; AI073871/AI/NIAID NIH HHS; AI083911/AI/NIAID NIH HHS; AI46629/AI/NIAID NIH HHS; CA34196/CA/NCI NIH HHS; DK089572/DK/NIDDK NIH HHS; HL077642/HL/NHLBI NIH HHS; P30 AI042845/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Stem Cell Factor
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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