Research Center for Immunology and Autoimmune Diseases, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
Mol Ther. 2010 Mar;18(3):625-34. doi: 10.1038/mt.2009.317. Epub 2010 Jan 19.
Respiratory diseases are a major cause of mortality and morbidity worldwide. Current treatments offer no prospect of cure or disease reversal. Transplantation of pulmonary progenitor cells derived from human embryonic stem cells (hESCs) may provide a novel approach to regenerate endogenous lung cells destroyed by injury and disease. Here, we examine the therapeutic potential of alveolar type II epithelial cells derived from hESCs (hES-ATIICs) in a mouse model of acute lung injury. When transplanted into lungs of mice subjected to bleomycin (BLM)-induced acute lung injury, hES-ATIICs behaved as normal primary ATIICs, differentiating into cells expressing phenotypic markers of alveolar type I epithelial cells. Without experiencing tumorigenic side effects, lung injury was abrogated in mice transplanted with hES-ATIICs, demonstrated by recovery of body weight and arterial blood oxygen saturation, decreased collagen deposition, and increased survival. Therefore, transplantation of hES-ATIICs shows promise as an effective therapeutic to treat acute lung injury.
呼吸系统疾病是全球范围内导致死亡和发病的主要原因。目前的治疗方法无法治愈或逆转疾病。从人胚胎干细胞(hESC)中衍生的肺祖细胞移植可能为内源性肺细胞提供一种新的再生方法,这些细胞被损伤和疾病破坏。在这里,我们在博来霉素(BLM)诱导的急性肺损伤小鼠模型中研究了源自 hESC 的肺泡 II 型上皮细胞(hES-ATIICs)的治疗潜力。当将 hES-ATIICs 移植到接受博来霉素(BLM)诱导的急性肺损伤的小鼠的肺部时,它们表现为正常的原发性 ATIIC,分化为表达肺泡 I 型上皮细胞表型标志物的细胞。在没有发生肿瘤副作用的情况下,接受 hES-ATIIC 移植的小鼠的肺损伤被消除,这表现为体重和动脉血氧饱和度恢复,胶原沉积减少和存活率增加。因此,hES-ATIIC 移植显示出作为有效治疗方法治疗急性肺损伤的潜力。