Transplantation of Human Embryonic Stem Cell-Derived Alveolar Epithelial Type II Cells Abrogates Acute Lung Injury in Mice
Transplantation of Human Embryonic Stem Cell-Derived Alveolar Epithelial Type II Cells Abrogates Acute Lung Injury in Mice
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DOI：
10.1038/mt.2009.317
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发表时间：
2010-03-01
影响因子：
12.4
通讯作者：
Wetsel, Rick A.
中科院分区：
文献类型：
--
作者：
Wang, Dachun;Morales, John E.;Wetsel, Rick A.
呼吸系统疾病是全世界死亡和发病的一个主要原因。目前的治疗方法没有治愈或逆转疾病的希望。来源于人胚胎干细胞（hESCs）的肺祖细胞移植可能为再生损伤和疾病破坏的内源性肺细胞提供了一种新的途径。在这里，我们研究了来自hESCs的肺泡II型上皮细胞（hES-ATIICs）在小鼠急性肺损伤模型中的治疗潜力。当移植到博来霉素（BLM）诱导的急性肺损伤小鼠的肺中时，hES-ATIICs表现为正常的原发ATIICs，分化为表达肺泡I型上皮细胞表型标记的细胞。在没有发生致瘤性副作用的情况下，移植hES-ATIICs小鼠的肺损伤被消除，表现为体重和动脉血氧饱和度恢复，胶原沉积减少，生存率提高。因此，hES-ATIICs移植有望成为治疗急性肺损伤的有效方法。
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.