利用内源性干细胞原位再生晶状体治疗婴幼儿白内障

Pediatric cataract therapy with endogenous stem cells-mediated lens regeneration

利用内源性干细胞进行组织器官的修复和再生是再生医学研究的最终目标。婴幼儿白内障是幼儿致盲性眼病的首要病因,目前尚无有效治疗手段。本研究组从哺乳动物内成功分离并获得了晶状体上皮干细胞,证明Pax6和Bmi1是维持其分化和自我更新的关键因子,并以保留内源性干细胞为目标,设计了全新的白内障术式。相较于传统术式,新术式最大程度地保留了内源性干细胞、基底膜和微环境,在新西兰兔、食蟹猴和先天性白内障患儿内实现了功能性晶状体的再生。研究结果为白内障提供了全新的治疗策略并为组织再生及内源性干细胞的应用提供了全新的范例。

Repair and regeneration of tissues using endogenous stem cells represent an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure may pose notable risks of complications. In this paper we isolate lens epithelial stem/progenitor cells（LECs） in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method for removal of cataract that preserves endogenous LECs and achieves functional regeneration of lens in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from the current practice, preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells.