Abstract
Introduction: Stem cell-based therapy is a promising approach for the treatment of idiopathic pulmonary fibrosis (IPF). We have previously demonstrated that lung-derived mesenchymal stem cells (MSC) exert anti-fibrotic effects in vitro . MSC enhanced epithelium wound repair via hepatocyte growth factor (HGF). In this study, we further investigated the effect of MSC on HGF-secretion in fibroblasts. Methods: MSC and fibroblasts were isolated from lung tissue obtained from patients with IPF. The effect of MSC conditioned medium (MSC-CM) on HGF-secretion and signaling pathway activation in fibroblasts were assessed by ELISA and western blotting; MSC-CM was analyzed using a cytokine array kit. Results: MSC-CM significantly induced HGF-secretion in fibroblasts. MSC-CM activated the mitogen activated protein (MAP) kinase p38 and nuclear factor kappa-B (NF-κB) in fibroblasts, suggesting a pro-inflammatory mediator. MSC-CM-induced HGF-secretion was significantly reduced by the inhibition of p38. Size-exclusion filtration of MSC-CM indicated that the mediator of the observed effect on HGF-secretion is smaller than 30 kDa. Cytokine array analysis of MSC-CM demonstrated several pro-inflammatory cytokines among the ten highest secreted proteins. Conclusions: Our data demonstrated that lung resident MSC induced the secretion of the anti-fibrotic growth factor HGF by fibroblasts in vitro and this effect was mediated via pro-inflammatory signaling pathways. Our data suggest that the anti-fibrotic properties of lung resident MSC are based - at least partly – on their interaction with surrounding structural cells. Funded by a Sinergia grant from the Swiss National Research Foundation.
Published Version
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