Transplantation of human embryonic stem cell-derived alveolar epithelial type II cells abrogates acute lung injury in mice.
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.
Wang
Dachun
D
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.
Morales
John E
JE
Calame
Daniel G
DG
Alcorn
Joseph L
JL
Wetsel
Rick A
RA
D055371:Acute Lung Injury / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology*; D004847:Epithelial Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D010100:Oxygen / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011650:Pulmonary Alveoli / Q000378:metabolism*; D033581:Stem Cell Transplantation / Q000379:methods; D014162:Transfection; D019076:Transgenes
D010100:Oxygen