Treatment with Mesenchymal Stromal Cells Improve Pathological Abnormalities in ARDS

Background: ARDS can occur either direct (pneumonia, aspi-ration, contusion) or indirect (sepsis, trauma, pancreatitis) lung injuries, but sepsis result in the majority of cases. The patho-genesis of ARDS is complex with loss of the alveolar-capillary barrier and flooding of the airspaces with protein-rich fluid; in-jury to the alveolar epithelium; an invasion of neutrophils and macrophages; and fibrin deposition. The complex pathogenesis of ARDS makes animal models a necessity in the study of this disorder. MSCs exert their beneficial effects by the release of paracrine factors, microvesicles, and transfer of mitochondria, all of which have pro-inflammatory and anti-inflammatory effects on injured lung endothelium and alveolar epithelium, including enhancing the resolution of pulmonary edema by upregulating alveolar fluid clearance. MSCs also have antimi-crobial effects mediated by the release of antimicrobial factors and by up-regulating monocyte/macrophage phagocytosis.Materials and Methods: Large animal model of ARDS was in-duced with a single intratracheal dose of lipopolysaccharide in 10 males Shall sheep. Then, in the treatment group, BM-MSCs were isolated and cultured and 5×107 cells were autographed and PBS was injected in the control group intratracheally. The sheep were sacrificed 7 days after transplantation. Then, the thoracic cavity was cut, and the lungs were ligatured, dissected and removed from the chest. First, the lungs were macroscopi-cally examined, and abnormalities were recorded. Then the tis-sue sections of the lungs were fixed in neutral-buffered formalin of 10%, the process was routinely done, stained with H&E and seen by Nikon Optical Microscope. Finally, the images were processed using AxioVision software, version 4.8.Results: Sections of the lung shown severe histopathological patterns in the control group compared to the treatment group as hemorrhage in parenchyma and alveoli, severe vascular hyper-emia and interstitial pneumonia, severe alveolar edema, inflam-mation and fibrin deposition, presence of hyaline membranes and intra-alveolar fibrin polymerization, polymorph nuclear leukocyte margination and sequestration in the capillary ves-sels, abundant presence of inflammatory cells, epithelial cells and other cell debris in interstitial spaces and alveoli and septal thickening inter-alveolar. But in the group recipients of BM-MSCs reduced the infiltration rate of inflammatory cells in in-tra-alveolar, hyperemia, hemorrhage, and edema or fibrin, and lungs structure were normal approximately and only slightly amount of thickness of the alveolar septum and edema wereseen.Conclusion: According to our clinical results, MSCs therapy could improve most of the pathological changes in this model of ADRS. In our opinion, MSC-based therapies have strong preclinical data demonstrating efficacy and can be scaled up for clinical use.

کلیدواژه ها:

Mesenchymal Stromal Cells ، ARDS ، Sheep ، Pathol-ogy ، Lung