Stem cells and cell therapy approaches in lung biology and diseases

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.

Abbreviations: AEC, alveolar epithelial cell, ALI, acute lung injury, ARDS, acute respiratory distress syndrome, BASC, bronchioalveolar stem cell, CCSP, Clara cell secretory protein, CF, cystic fibrosis, CFTR, cystic fibrosis transmembrane conductance regulator, CLP, cecal ligation and puncture, COPD, chronic obstructive pulmonary disease, eNOS, endothelial nitric oxide synthetase, EPC, endothelial progenitor cell, ESC, embryonic stem cell, FEV1, forced expiratory volume in 1 second, FVC, forced vital capacity, GFP, green fluorescent protein, HSC, hematopoietic stem cell, IPF, idiopathic pulmonary fibrosis, KGF, keratinocyte growth factor, LPS, lipopolysaccharide, MCT, monocrotaline, MHC, major histocompatibility complex, MSC, mesenchymal stromal (stem) cell, PH, pulmonary hypertension, pro-SPC, pro-surfactant protein C, Sca-1, stem cell antigen-1