Transplantation of Human Embryonic Stem Cell-Derived Alveolar Epithelial Type II Cells Abrogates Acute Lung Injury in Mice

被引:113
作者
Wang, Dachun [1 ]
Morales, John E. [1 ]
Calame, Daniel G. [1 ,2 ]
Alcorn, Joseph L. [3 ,4 ]
Wetsel, Rick A. [1 ,4 ,5 ]
机构
[1] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med Prevent Human Dis, Res Ctr Immunol & Autoimmune Dis, Houston, TX 77030 USA
[2] Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX USA
[3] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA
[4] Univ Texas Med Sch Houston, Dept Biochem & Mol Biol, Houston, TX USA
[5] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med Prevent Human Dis, Dev Biol Lab, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
BONE-MARROW; PULMONARY EPITHELIUM; ENGRAFTMENT; BLEOMYCIN; GENE; DIFFERENTIATION; EXPRESSION; FIBROSIS; IDENTIFICATION; LOCALIZATION;
D O I
10.1038/mt.2009.317
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:625 / 634
页数:10
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