Influence of secretome from porcine cardiosphere-derived cells on porcine macrophage polarization and their possible implications for cardiac remodeling post-myocardial infarction in vitro

Maria Pulido¹María de los Ángeles De Pedro^1,2Ana María Marchena^1,2Verónica Álvarez Pérez¹Javier G Casado^2,3,4Francisco Miguel Sanchez Margallo^1,2*Esther López Nieto^1,2

• ¹Stem Cell Therapy Unit, Jesus Uson Minimally Invasive Surgery Centre, Cáceres, Spain
• ²RICORS-TERAV Network, Madrid, Spain
• ³Immunology Unit, University of Extremadura, Cáceres, Spain
• ⁴Institute of Molecular Pathology Biomarkers, University of Extremadura, Cáceres, Spain

The inflammatory response plays a crucial role in tissue repair following myocardial infarction (MI), with macrophages being central regulators of inflammation and tissue remodeling. Macrophage polarization between pro-inflammatory M1 and anti-inflammatory M2 phenotypes significantly influences inflammation and tissue repair. In this study, we investigate the effect of the secretome from porcine cardiosphere-derived cells (S-CDCs) on macrophage polarization, and its subsequent impact on endothelial cells (HUVECs) and cardiac fibroblasts (PCFs), both key players in tissue regeneration post-MI. Our results demostrate suggest that S-CDCs may induce a mixed M1/M2 phenotype in macrophages, potentially reducing the inflammatory effect profile of the M1 phenotype without fully promoting a M2 phenotype. Conditioned medium from S-CDCtreated M1 macrophages exhibited significant pro-angiogenic effects, including enhanced migration and wound healing in HUVECs, whereas conditioned medium from M2 treated macrophages did not elicit similar effects. Additionally, conditioned medium from S-CDC-treated M1 macrophages modulates the migratory and fibrotic activity of PCFs, suggesting a potencial role in cardiac remodeling. Transcriptomic analysis in S-CDCs revealed a cytokine profile enriched in pro-reparative factors such as VEGFA, TGFB, and CCL2, which may contribute to tissue repair and angiogenesis while limiting excessive inflammation indicating that the S-CDCs promotes tissue repair and angiogenesis while minimizing excessive inflammation. These findings propose S-CDCs as a promising therapeutic strategy to enhance cardiac repair following MI by modulating macrophage polarization and promoting tissue regeneration. These findings support the potential of S-CDCs as a supportive strategy for modulating macrophage response and influencing cardiac tissue regeneration.Con formato: Espacio Después: 0 pto Con formato: Inglés (Estados Unidos