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  • Title: Human Mesenchymal Stem Cell Secretome from Bone Marrow or Adipose-Derived Tissue Sources for Treatment of Hypoxia-Induced Pulmonary Epithelial Injury.
    Author: Shologu N, Scully M, Laffey JG, O'Toole D.
    Journal: Int J Mol Sci; 2018 Sep 30; 19(10):. PubMed ID: 30274394.
    Abstract:
    UNLABELLED: : Alveolar epithelial dysfunction induced by hypoxic stress plays a significant role in the pathological process of lung ischemia-reperfusion injury (IRI). Mesenchymal stem cell (MSC) therapies have demonstrated efficacy in exerting protective immunomodulatory effects, thereby reducing airway inflammation in several pulmonary diseases. AIM: This study assesses the protective effects of MSC secretome from different cell sources, human bone marrow (BMSC) and adipose tissue (ADSC), in attenuating hypoxia-induced cellular stress and inflammation in pulmonary epithelial cells. METHODS: Pulmonary epithelial cells, primary rat alveolar epithelial cells (AEC) and A549 cell line were pre-treated with BMSC, or ADSC conditioned medium (CM) and subjected to hypoxia for 24 h. RESULTS: Both MSC-CM improved cell viability, reduced secretion of pro-inflammatory mediators and enhanced IL-10 anti-inflammatory cytokine production in hypoxic injured primary rat AECs. ADSC-CM reduced hypoxic cellular injury by mechanisms which include: inhibition of p38 MAPK phosphorylation and nuclear translocation of subunits in primary AECs. Both MSC-CM enhanced translocation of Bcl-2 to the nucleus, expression of cytoprotective glucose-regulated proteins (GRP) and restored matrix metalloproteinases (MMP) function, thereby promoting repair and cellular homeostasis, whereas inhibition of GRP chaperones was detrimental to cell survival. CONCLUSIONS: Elucidation of the protective mechanisms exerted by the MSC secretome is an essential step for maximizing the therapeutic effects, in addition to developing therapeutic targets-specific strategies for various pulmonary syndromes.
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