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Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible fibrotic lung disease, resulting in respiratory insufficiency and reduced survival. Pulmonary fibrosis is a result of repeated alveolar epithelial microinjuries, followed by abnormal regeneration and repair processes in the lung. Recently, stem cells and their secretome have been investigated as a novel therapeutic approach in pulmonary fibrosis. We evaluated the potential of induced pluripotent stem cells (iPSC) conditioned media (iPSC-cm) to regenerate and repair the alveolar epithelium  in vitro  and improve bleomycin induced lung injury  in vivo .    Methods  IPSC-cm was collected from cultured iPSC derived from human foreskin fibroblasts and its biological effects on alveolar epithelial wound repair was studied in an alveolar wound healing assay  in vitro . Furthermore, iPSC-cm was intratracheally instilled 7 days after bleomycin induced injury in the rat lungs and histologically and biochemically assessed 7 days after instillation.    Results  iPSC-cm increased alveolar epithelial wound repair  in vitro  compared with medium control. Intratracheal instillation of iPSC-cm in bleomycin-injured lungs reduced the collagen content and improved lung fibrosis in the rat lung  in vivo . Profibrotic TGFbeta1 and α-smooth muscle actin (α-sma) expression were markedly reduced in the iPSC-cm treated group compared with control. Antifibrotic hepatocyte growth factor (HGF) was detected in iPSC-cm in biologically relevant levels, and specific inhibition of HGF in iPSC-cm attenuated the antifibrotic effect of iPSC-cm, indicating a central role of HGF in iPSC-cm.    Conclusion  iPSC-cm increased alveolar epithelial wound repair  in vitro  and attenuated bleomycin induced fibrosis  in vivo , partially due to the presence of HGF and may represent a promising novel, cell free therapeutic option against lung injury and fibrosis.    Electronic supplementary material  The online version of this article (doi:10.1186/scrt513) contains supplementary material, which is available to authorized users.

The secretome of induced pluripotent stem cells reduces lung fibrosis in part by hepatocyte growth factor