慢性阻塞性肺疾病(COPD)以持续性气流受限为特征，主要原因之一是炎症过程造成肺实质破坏，肺泡和小气道塌陷，使得肺弹性收缩力下降。仅靠药物治疗很难逆转这一现象。II型肺泡上皮细胞(ATII)被认为是肺泡上皮的前体细胞，其增殖和转化与肺泡的损伤修复关系密切。目前还没有研究尝试通过ATII细胞移植来修复COPD的肺损伤。近年来，ATII细胞在体外陆续由胚胎干细胞、诱导的多能干细胞和各种间充质干细胞分化而来。但其普遍的不足是分化效率低、混杂有各阶段的前体细胞，有致畸胎瘤的风险。本研究拟采用经定点基因改造的小鼠胚胎干细胞(mESC)来源的高纯度ATII细胞(mESC-ATII)，通过气管内插管移植给熏烟造成COPD的小鼠，观察对肺损伤的修复作用，并探讨其对炎性细胞浸润、细胞凋亡和氧化损伤的影响，为开辟新的COPD的再生治疗策略提供实验基础。

Chronic obstructive pulmonary disease (COPD) is characterized by a persistent airflow limitation. Reduction of the elastic recoil of the lung through the collapse of alveoli and small airways by parenchymal destruction is one of the major reasons, but no effective treatment is available to alleviate or reverse this destruction. As the progenitor cells of alveolar epithelium, alveolar type II epithelial cells (ATII) are particularly crucial during the restoration of damaged alveoli after injury. However, no researchers has tried to repair the pulmonary injuries in COPD through ATII cells transplantation. Recently, ATII cells have been differentiated from embryonic stem cells (ESCs), induced pluripotent stem cells and mesenchymal stem cells respectively, however, these procedures are not efficient, generating only a very small percentage of ATII cells mixed with many pluripotent cells in different stage of differentiation, which carries a significant risk of producing teratomas after transplantation in vivo. To explore new regenerative therapeutic strategies for COPD, this proposal tries to use a pure population of ATII cells derived from a site-specifically genetically modified mESC line to repair the pulmonary injuries in COPD by intratracheal transplantation, and investigate the effects on inflammatory cell infiltration, cell apoptosis and oxidative damage.