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An Immune System-Modified Rat Model for Human Stem Cell Transplantation Research.

ABSTRACT: Due to its lack of both innate and acquired immune responses to human cells, the NODSCIDIl2r?-/- (NSG) mouse model has become an important tool for human stem cell research. When compared with the mouse, the rat is physiologically more similar to humans and offers advantages in preclinical efficacy studies on human stem cells, particularly in evaluating neural, hepatic, and cardiac functions. Therefore, we generated a human SIRP?+Prdkc-/-Il2r?-/- rat model, denoted NSG-like (NSGL) rat, which expresses human SIRP? and is abolished in the development of B, T, and natural killer cells. When compared with Prdkc-/-Il2r?-/- (SG) rats, NSGL rats allow more efficient engraftment of human cancer cells and human pluripotent stem cells. In addition, only NSGL rats, but not SG rats, can be engrafted with human hematopoietic stem cells to reconstitute the human immune system. Therefore, NSGL rats represent an improved xenotransplantation model for efficacy studies of human stem cells.

SUBMITTER: Yang X 

PROVIDER: S-EPMC6092637 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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An Immune System-Modified Rat Model for Human Stem Cell Transplantation Research.

Yang Xinglong X   Zhou Jianlong J   He Jingjin J   Liu Jingfeng J   Wang Hui H   Liu Yachen Y   Jiang Tao T   Zhang Qianbing Q   Fu Xuemei X   Xu Yang Y  

Stem cell reports 20180705 2

Due to its lack of both innate and acquired immune responses to human cells, the NODSCIDIl2rγ<sup>-/-</sup> (NSG) mouse model has become an important tool for human stem cell research. When compared with the mouse, the rat is physiologically more similar to humans and offers advantages in preclinical efficacy studies on human stem cells, particularly in evaluating neural, hepatic, and cardiac functions. Therefore, we generated a human SIRPα<sup>+</sup>Prdkc<sup>-/-</sup>Il2rγ<sup>-/-</sup> rat m  ...[more]

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