Hypoxia-preconditioned mesenchymal stem cells attenuate bleomycin-induced pulmonary fibrosis

摘要: Idiopathic pulmonary fibrosis is a progressive diffuse parenchymal lung disorder of unknown etiology. Mesenchymal stem cell (MSC)-based therapy novel approach with great therapeutic potential for the treatment diseases. Despite demonstration MSC grafting, populations engrafted MSCs have been shown to decrease dramatically 24 hours post-transplantation due exposure harsh microenvironments. Hypoxia known induce expression cytoprotective genes and also secretion anti-inflammatory, anti-apoptotic anti-fibrotic factors. Hypoxic preconditioning thought enhance potency duration survival MSCs. In this work, we aimed prolong effectiveness idiopathic transplantation by use hypoxia-preconditioned was achieved in under an optimal hypoxic environment. The levels factors their biological effects on damaged alveolar epithelial cells or transforming growth factor-beta 1-treated fibroblast were studied co-culture experiments vitro. Furthermore, (HP-MSCs) intratracheally instilled into bleomycin-induced mice at day 3, functions, cellular, molecular pathological changes assessed 7 21 days after bleomycin administration. pro-survival, anti-apoptotic, anti-oxidant upregulated conditions. MRC-5 cells, attenuated extracellular matrix production through paracrine effects. respiratory functions significantly improved up 18 treatment. Expression inflammatory fibrotic factor all downregulated tissues MSC-treated mice. Histopathologic examination observed significant amelioration fibrosis. Several LacZ-labeled within lungs groups 21, but no signals detected normoxic group. Our data further demonstrated that upregulation hepatocyte possibly played important role mediating transplanted Transplantation exerted better enhanced rate MSCs, partially factor.