西亚试剂：An Effective Approach to Prevent Immune Rejection of Human

An Effective Approach to Prevent Immune Rejection of Human ESC-Derived Allografts

Zhili Rong， Meiyan Wang， Zheng Hu， Martin Stradner， Shengyun Zhu， Huijuan Kong， Huanfa Yi， Ananda Goldrath， Yong-Guang Yang， Yang Xu， Xuemei Fu

Human embryonic stem cells (hESCs) hold great promise for cell therapy as a source of diverse differentiated cell types. One key bottleneck to realizing such potential is allogenic immune rejection of hESC-derived cells by recipients. Here， we optimized humanized mice (Hu-mice) reconstituted with a functional human immune system that mounts a vigorous rejection of hESCs and their derivatives. We established knockin hESCs that constitutively express CTLA4-Ig and PD-L1 before and after differentiation， denoted CP hESCs. We then demonstrated that allogenic CP hESC-derived teratomas， fibroblasts， and cardiomyocytes are immune protected in Hu-mice， while cells derived from parental hESCs are effectively rejected. Expression of both CTLA4-Ig， which disrupts T cell costimulatory pathways， and PD-L1， which activates T cell inhibitory pathway， is required to confer immune protection， as neither was sufficient on their own. These findings are instrumental for developing a strategy to protect hESC-derived cells from allogenic immune responses without requiring systemic immune suppression.

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