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Proteomic profile on remote myocardium after administration of secretome from menstrual blood derived cells in swine infarct model

M Pulido(1) M A de Pedro(1,2) V Álvarez(1) F M Sánchez-Margallo(1,2) J G Casado(2,3,4) E López(1,2)

1:Centro de Cirugía de Mínima Invasión Jesús Usón; 2:RICORS-TERAV Network; 3:Immunology Unit, University of Extremadura; 4:Institute of Molecular Pathology Biomarkers, University of Extremadura

The swine model of myocardial infarction is a great animal model to mimic this pathology and evaluate the efficacy of different therapies. After myocardial infarction induction, proteomic changes are developed in the remote and infarcted myocardium, contributing to the pathogenesis and the poor prognosis. In this scenario, the evaluation of stem cell therapy effects let shed light on new therapeutic strategies. Therefore, in this work, we improve the therapeutic potential of menstrual blood stromal cells (MenSCs) by priming with IFNγ and TNFα (MenSCs*) and evaluate its effect on remote myocardium after their secretome administration (S-MenSCs*). For this purpose, myocardial infarctions were generated induced by 90-min balloon occlusion of the mid-LAD. Then, and by intrapericardial administration, animals received S-MenSCs* (AMI/S-MenSCs*, n = 4) and vehicle (AMI/Placebo, n = 4). Seven days post-therapy, hearts were harvested and infarcted tissues were collected for proteomic analyses. Comparative results showed 64 genes differentially expressed (FDR  < .05) after S-MenSCs* treatment in remote myocardium. STRING web tool was used for functional enrichment analysis, revealing that differentially expressed genes are related to Gene Ontology Biological Process and Reactome Pathways such as Muscle contraction (GO:0006936), Striated muscle contraction (GO:0006941, SSC-390522) (FDR  < .05). These results suggest that the secretome content of MenSCs* could regulate the gene expression of protein related to contractile fibers of cardiac tissue, contributing to alleviate cardiac disfunction. In conclusion, the therapeutic potential of S-MenSCs* in remote myocardium of myocardial infarction patients may reduce cardiac remodeling and so, improving their prognosis.

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