一個不需要預輻射照處理的免疫缺陷小鼠模型: Engraftment of human HSC in non-irradiated newborn NOD-scid IL2rγnull mice is enhanced by transgenic expression of membrane-bound human SCF.

一個新的使用免疫缺陷小鼠模型(immunodeficient mouse model)的方法: 不需要預輻射照處理 (pre-irradiation treatment)也可以移植入人類臍帶血造血幹細胞(Cord Blood HSC), 供應人類造血和免疫系統模型作臨床前研究(translational research).

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Blood. 2012 Jan 12. [Epub ahead of print]

Engraftment of human HSC in non-irradiated newborn NOD-scid IL2rγnull mice is enhanced by transgenic expression of membrane-bound human SCF.

Brehm MA, Racki WJ, Leif J, Burzenski L, Hosur V, Wetmore A, Gott B, Herlihy M, Ignotz R, Dunn R, Shultz LD, Greiner DL.

Source

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States;

Abstract

Immunodeficient mice engrafted with human hematopoietic stem cells (HSC) support multi-disciplinary 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 gamma chain (IL2rg) gene, including NOD-scid IL2rγ(null) (NSG) mice. Engraftment of human HSC requires pre-conditioning 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 non-irradiated NSG mice and eliminate complications associated with irradiation. Surprisingly, detectable levels of human CD45+ cell chimerism were observed following transplantation of cord blood-derived human HSC into non-irradiated 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, non-irradiated NSG-Tg(hu-mSCF) mice engrafted as newborns with human HSC 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 pre-conditioning for human HSC engraftment and immune system development.

PMID:

 

22246028

 

[PubMed - as supplied by publisher]