Division of Pulmonary, Critical Care and Allergy, Department of Medicine, Emory University, Atlanta, GA, USA.
Transl Res. 2010 Sep;156(3):188-205. doi: 10.1016/j.trsl.2010.06.007. Epub 2010 Jul 7.
Cell-based therapies with embryonic or adult stem cells, including induced pluripotent stem cells, have emerged as potential novel approaches for several devastating and otherwise incurable lung diseases, including emphysema, pulmonary fibrosis, pulmonary hypertension, and the acute respiratory distress syndrome. Although initial studies suggested engraftment of exogenously administered stem cells in lung, this is now generally felt to be a rare occurrence of uncertain physiologic significance. However, more recent studies have demonstrated paracrine effects of administered cells, including stimulation of angiogenesis and modulation of local inflammatory and immune responses in mouse lung disease models. Based on these studies and on safety and initial efficacy data from trials of adult stem cells in other diseases, groundbreaking clinical trials of cell-based therapy have been initiated for pulmonary hypertension and for chronic obstructive pulmonary disease. In parallel, the identity and role of endogenous lung progenitor cells in development and in repair from injury and potential contribution as lung cancer stem cells continue to be elucidated. Most recently, novel bioengineering approaches have been applied to develop functional lung tissue ex vivo. Advances in each of these areas will be described in this review with particular reference to animal models.
基于胚胎或成体干细胞的细胞疗法，包括诱导多能干细胞，已成为多种致命性和其他不可治愈的肺部疾病的潜在新方法，包括肺气肿、肺纤维化、肺动脉高压和急性呼吸窘迫综合征。尽管最初的研究表明外源性给予的干细胞在肺部的植入，但现在普遍认为这是一种罕见的、不确定具有生理意义的情况。然而，最近的研究表明，给予的细胞具有旁分泌作用，包括刺激血管生成和调节小鼠肺部疾病模型中的局部炎症和免疫反应。基于这些研究以及其他疾病中成人干细胞的安全性和初步疗效数据，已经启动了针对肺动脉高压和慢性阻塞性肺疾病的细胞疗法的开创性临床试验。与此同时，内源性肺祖细胞在发育和损伤修复中的作用及其作为肺癌干细胞的潜在贡献也在不断被阐明。最近，新的生物工程方法已被应用于体外开发功能性肺组织。本文将介绍这些领域的进展，特别参考动物模型。
