子宫内膜损伤常导致宫腔粘连，致不孕不育或流产，目前临床上尚无有效治疗方法。应用干细胞进行子宫内膜上皮层再生修复，无法避免诱导分化过程，而干细胞都具有跨谱系分化特性，定向诱导分化非常困难。最新报道的条件重编程（CR）技术，从病人自体微量样本获得CR细胞，在体外快速增殖并保持正常生物学特性和谱系分化潜能，无需诱导即可正常分化和发育。前期我们与该技术的发明人合作，成功建立了第一株中国人子宫内膜CR细胞，以及小鼠子宫内膜CR细胞。本申请项目将在此基础上，进一步鉴定人和小鼠子宫内膜CR细胞的正常生物学特性。通过基质胶和气液界面3D培养、小鼠肾小囊下移植，鉴定CR细胞分化发育为功能性子宫内膜的潜能。再利用子宫内膜CR细胞进行小鼠子宫内膜损伤所致宫腔粘连的再生修复。本项目旨在为临床上高发难治性宫腔粘连的治疗提供新的策略，为今后进行病人来源子宫内膜CR细胞自体移植修复宫腔粘连的临床应用提供实验和理论依据。

Intrauterine adhesion (IUA) results from severe damage to the basal layer of endometrium. This disease often leads to infertility or recurrent pregnancy loss. There is no specific treatment available for IUA patients. The use of embronic stem cells or mesencyhmal stem cells for the endometrial regeneration might have potential but need a complicated process for differentiation. It has been very difficult to establish/develop a reproducible and practicable protocol for cell differentiation. Most recently, a novel cell technology, named “conditional reprogramming (CR) technology ”, can establish patient-derived epithelial cells cultures that have the capacity to grow rapidly and indefinitely without genetic manipulation. These CR cells possess the normal biology characteristics and maintain lineage-differentiation potential. We collaborated with the CR inventors and have established the first normal CR endometrial cells originated from Chinese (Han population), and murine endometrial CR cells as well. We will characterize the normal biological features of these two CR cells. And we will define the capacity of CR cells to differentiate and develop into functional endometrium without inducing protocols by matriGel 3D culture, air-liquid interface 3D culture and kidney renal capsule transplantation. More importantly, we will treat murine IUA disease by using endometrial CR cells, thereby providing a new strategy and model for the preclinical treatment of IUA using patient-derived CR cells.