Isolation of alveolar epithelial type II progenitor cells from adult human lungs.
Isolation of alveolar epithelial type II progenitor cells from adult human lungs.
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DOI：
10.1038/labinvest.2010.187
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发表时间：
2011-03
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肺中驻留的干细胞/祖细胞对组织内稳态和修复非常重要。然而，成人肺中的肺泡II型(ATII)细胞的祖细胞群体尚未确定。本研究的目的是从成人肺中分离出具有分化为ATII细胞能力的祖细胞。我们分离出具有自我更新能力和在体外产生ATII细胞的集落形成细胞。这些未分化的祖细胞分别表达间充质干细胞(MSCs)的表面标志和与ATII细胞相关的表面活性蛋白，如CD90和前表面活性蛋白C(Pro-SP-C)。基因芯片分析表明，与骨髓MSCs相比，与肺发育相关的转录本在前SP-C+/CD90+细胞中丰富。此外，病理检查显示，正常肺泡壁内有SP-C和CD90双阳性细胞，ATII细胞增生期肺泡上皮修复作用明显增强。我们的发现表明，成人肺含有ATII细胞的祖细胞群。这项研究是更好地理解成人肺泡干细胞生物学的第一步。
Resident stem/progenitor cells in the lung are important for tissue homeostasis and repair. However, a progenitor population for alveolar type II (ATII) cells in adult human lungs has not been identified. The aim of this study is to isolate progenitor cells from adult human lungs with the ability to differentiate into ATII cells. We isolated colony-forming cells that had the capability for self-renewal and the potential to generate ATII cells in vitro. These undifferentiated progenitor cells expressed surface markers of mesenchymal stem cells (MSCs) and surfactant proteins associated with ATII cells, such as CD90 and pro-surfactant protein-C (pro-SP-C), respectively. Microarray analyses indicated that transcripts associated with lung development were enriched in the pro-SP-C+/CD90+ cells compared with bone marrow-MSCs. Furthermore, pathological evaluation indicated that pro-SP-C and CD90 double-positive cells were present within alveolar walls in normal lungs, and significantly increased in ATII cell hyperplasias contributing to alveolar epithelial repair in damaged lungs. Our findings demonstrated that adult human lungs contain a progenitor population for ATII cells. This study is a first step toward better understanding of stem cell biology in adult human lung alveoli.