Autologous transplantation of thecal stem cells restores ovarian function in nonhuman primates
Hong Chen, Kai Xia, Weijun Huang, Huijian Li, Chao Wang, Yuanchen Ma, Jianhui Chen, Peng Luo, Shuwei Zheng, Jiancheng Wang, Yi Wang, Lin Dong, Zhipeng Tan, Xingqiang Lai, Frank Fuxiang Mao, Weiqiang Li, Xiaoyan Liang, Tao Wang, Andy Peng Xiang, Qiong Ke
Abstract
Premature ovarian insufficiency (POI) is defined as the loss of ovarian activity under the age of 40. Theca cells (TCs) play a vital role during folliculogenesis and TCs dysfunction participate in the pathogenesis of POI. Therefore, transplantation of thecal stem cells (TSCs), which are capable of self-renewal and differentiation into mature TCs, may provide a new strategy for treating POI. To investigate the feasibility, safety, and efficacy of TSCs transplantation in clinically relevant non-human primate (NHP) models, we isolate TSCs from cynomolgus monkeys, and these cells are confirmed to expand continuously and show potential to differentiate into mature TCs. In addition, engraftment of autologous TSCs into POI monkeys significantly improves hormone levels, rescues the follicle development, promotes the quality of oocytes and boosts oocyte maturation/fertilization rate. Taken together, these results for the first time suggest that autologous TSCs can ameliorate POI symptoms in primate models and shed new light on developing stem cell therapy for POI.