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Open AccessArticle

Human Mesenchymal Stem Cell Secretome from Bone Marrow or Adipose-Derived Tissue Sources for Treatment of Hypoxia-Induced Pulmonary Epithelial Injury

1
The Discipline of Anesthesia and Lung Biology Group, National University of Ireland Galway, H91 TK33 Galway, Ireland
2
Critical Care Medicine and Intensive Care, University Hospital Galway, H91 YR71 Galway, Ireland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(10), 2996; https://doi.org/10.3390/ijms19102996
Received: 27 July 2018 / Revised: 20 September 2018 / Accepted: 27 September 2018 / Published: 30 September 2018
(This article belongs to the Special Issue Adipose Stem Cells)
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. View Full-Text
Keywords: mesenchymal stem cells; MSC therapy; MSC conditioned medium; hypoxia; hypoxia-reoxygenation; lung ischemia-reperfusion; alveolar epithelial cells; heat shock proteins; glucose-regulated proteins; acute lung injury mesenchymal stem cells; MSC therapy; MSC conditioned medium; hypoxia; hypoxia-reoxygenation; lung ischemia-reperfusion; alveolar epithelial cells; heat shock proteins; glucose-regulated proteins; acute lung injury
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Shologu, N.; Scully, M.; Laffey, J.G.; O’Toole, D. Human Mesenchymal Stem Cell Secretome from Bone Marrow or Adipose-Derived Tissue Sources for Treatment of Hypoxia-Induced Pulmonary Epithelial Injury. Int. J. Mol. Sci. 2018, 19, 2996.

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