Intrapericardial Administration of Secretomes from Menstrual Blood-Derived Mesenchymal Stromal Cells: Effects on Immune-Related Genes in a Porcine Model of Myocardial Infarction
María Ángeles de Pedro,
María Pulido,
Federica Marinaro,
Verónica Álvarez,
Claudia Báez-Díaz,
Virginia Blanco,
Juan Carlos Silla-Castro,
Fátima Sanchez-Cabo,
Francisco Miguel Sánchez-Margallo,
Verónica Crisóstomo,
Javier G. Casado,
Esther López
Affiliations
María Ángeles de Pedro
Stem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, Carretera Nacional 521, Km 41.8-10071, 10004 Cáceres, Spain
María Pulido
Stem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, Carretera Nacional 521, Km 41.8-10071, 10004 Cáceres, Spain
Federica Marinaro
Stem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, Carretera Nacional 521, Km 41.8-10071, 10004 Cáceres, Spain
Verónica Álvarez
Stem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, Carretera Nacional 521, Km 41.8-10071, 10004 Cáceres, Spain
Claudia Báez-Díaz
Stem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, Carretera Nacional 521, Km 41.8-10071, 10004 Cáceres, Spain
Virginia Blanco
Stem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, Carretera Nacional 521, Km 41.8-10071, 10004 Cáceres, Spain
Juan Carlos Silla-Castro
Bioinformatics Unit, Centro Nacional de Investigaciones Cardiovasculares, C. de Melchor Fernández Almagro, 3, 28029 Madrid, Spain
Fátima Sanchez-Cabo
Bioinformatics Unit, Centro Nacional de Investigaciones Cardiovasculares, C. de Melchor Fernández Almagro, 3, 28029 Madrid, Spain
Francisco Miguel Sánchez-Margallo
Stem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, Carretera Nacional 521, Km 41.8-10071, 10004 Cáceres, Spain
Verónica Crisóstomo
Stem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, Carretera Nacional 521, Km 41.8-10071, 10004 Cáceres, Spain
Javier G. Casado
CIBER de Enfermedades Cardiovasculares (CIBERCV), C. de Melchor Fernández Almagro, 3, 28029 Madrid, Spain
Esther López
Stem Cell Therapy Unit, Jesús Usón Minimally Invasive Surgery Centre, Carretera Nacional 521, Km 41.8-10071, 10004 Cáceres, Spain
Acute myocardial infarction (AMI) is a manifestation of ischemic heart disease where the immune system plays an important role in the re-establishment of homeostasis. We hypothesize that the anti-inflammatory activity of secretomes from menstrual blood-derived mesenchymal stromal cells (S-MenSCs) and IFNγ/TNFα-primed MenSCs (S-MenSCs*) may be considered a therapeutic option for the treatment of AMI. To assess this hypothesis, we have evaluated the effect of S-MenSCs and S-MenSCs* on cardiac function parameters and the involvement of immune-related genes using a porcine model of AMI. Twelve pigs were randomly divided into three biogroups: AMI/Placebo, AMI/S-MenSCs, and AMI/S-MenSCs*. AMI models were generated using a closed chest coronary occlusion-reperfusion procedure and, after 72 h, the different treatments were intrapericardially administered. Cardiac function parameters were monitored by magnetic resonance imaging before and 7 days post-therapy. Transcriptomic analyses in the infarcted tissue identified 571 transcripts associated with the Gene Ontology term Immune response, of which 57 were differentially expressed when different biogroups were compared. Moreover, a prediction of the interactions between differentially expressed genes (DEGs) and miRNAs from secretomes revealed that some DEGs in the infarction area, such as STAT3, IGFR1, or BCL6 could be targeted by previously identified miRNAs in secretomes from MenSCs. In conclusion, the intrapericardial administration of secretome early after infarction has a significant impact on the expression of immune-related genes in the infarcted myocardium. This confirms the immunomodulatory potential of intrapericardially delivered secretomes and opens new therapeutic perspectives in myocardial infarction treatment.
