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

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

来源：Cell Stem Cell, 2014, 14(1): 121-130.

DOI：10.1016/j.stem.2013.11.014

• EMBRYONIC STEM-CELLS
• SUICIDE GENE
• HEMATOPOIETIC PRECURSORS
• RENAL-TRANSPLANTATION
• STROMAL CELLS
• TOLERANCE
• SYSTEM
• MICE
• THERAPY
• MOUSE

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.

• 出版日期2014-1-2
• 单位吉林大学; 深圳市儿童医院; 重庆医科大学