Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible fibrotic lung disease, resulting in\nrespiratory insufficiency and reduced survival. Pulmonary fibrosis is a result of repeated alveolar epithelial\nmicroinjuries, followed by abnormal regeneration and repair processes in the lung. Recently, stem cells and their\nsecretome have been investigated as a novel therapeutic approach in pulmonary fibrosis. We evaluated the\npotential of induced pluripotent stem cells (iPSC) conditioned media (iPSC-cm) to regenerate and repair the\nalveolar epithelium in vitro and improve bleomycin induced lung injury in vivo.\nMethods: IPSC-cm was collected from cultured iPSC derived from human foreskin fibroblasts and its biological\neffects on alveolar epithelial wound repair was studied in an alveolar wound healing assay in vitro. Furthermore,\niPSC-cm was intratracheally instilled 7 days after bleomycin induced injury in the rat lungs and histologically and\nbiochemically assessed 7 days after instillation.\nResults: iPSC-cm increased alveolar epithelial wound repair in vitro compared with medium control. Intratracheal\ninstillation of iPSC-cm in bleomycin-injured lungs reduced the collagen content and improved lung fibrosis in the\nrat lung in vivo. Profibrotic TGFbeta1 and ?-smooth muscle actin (?-sma) expression were markedly reduced in the\niPSC-cm treated group compared with control. Antifibrotic hepatocyte growth factor (HGF) was detected in\niPSC-cm in biologically relevant levels, and specific inhibition of HGF in iPSC-cm attenuated the antifibrotic effect of\niPSC-cm, indicating a central role of HGF in iPSC-cm.\nConclusion: iPSC-cm increased alveolar epithelial wound repair in vitro and attenuated bleomycin induced fibrosis\nin vivo, partially due to the presence of HGF and may represent a promising novel, cell free therapeutic option\nagainst lung injury and fibrosis.
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