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

  • Stem Cell Reports. 2018 Aug 14;11(2):514-521. doi: 10.1016/j.stemcr.2018.06.004.
Xinglong Yang  1 ,  Jianlong Zhou  1 ,  Jingjin He  2 ,  Jingfeng Liu  3 ,  Hui Wang  4 ,  Yachen Liu  1 ,  Tao Jiang  3 ,  Qianbing Zhang  1 ,  Xuemei Fu  5 ,  Yang Xu  6
Affiliations
  • 1. Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
  • 2. Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China; The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong 518033, China.
  • 3. Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • 4. The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong 518033, China.
  • 5. The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong 518033, China. Electronic address: [email protected].
  • 6. Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China; The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong 518033, China; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: [email protected].
PMID: 29983387 DOI: 10.1016/j.stemcr.2018.06.004
Abstract

Due to its lack of both innate and acquired immune responses to human cells, the NODSCIDIl2rγ-/- (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+Prdkc-/-Il2rγ-/- rat model, denoted NSG-like (NSGL) rat, which expresses human SIRPα and is abolished in the development of B, T, and natural killer cells. When compared with Prdkc-/-Il2rγ-/- (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.

Keywords
acquired immunity; hematopoietic stem cells; human stem cells; immunodeficient rat models; innate immunity.
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