Secretome from porcine cardiosphered derived-cells decreased the pro-inflammatory profile of porcine M1 macrophages in vitro

M Pulido(1) M A de Pedro(1,2) V Álvarez(1) F M Sánchez-Margallo(1,2,3) J G Casado(2,3,4,5) E López(1,2)

1:Centro de Cirugía de Mínima Invasión Jesús Usón; 2:RICORS-TERAV Network; 3:CIBER of Cardiovascular Diseases (CIBERCV); 4:Immunology Unit, Department of Physiology, University of Extremadura; 5:Institute of Molecular Pathology Biomarkers, University of Extremadura

Activated macrophages are usually divided into M1 (pro-inflammatory profile) and M2 (anti-inflammatory profile), based on surface marker expression and cytokine secretion. Both are related to inflammatory diseases such as myocardial infarction (AMI), being key in both the initial inflammatory response and subsequent wound healing. However, the prolonged presence of M1 can lead to expansion of the infarcted area, thus delaying the repair phase.

Administration of the secretome from stromal cells has been suggested as a promising therapeutic approach for inflammatory diseases, as they appear to ameliorate the inflammatory environment by modulating the activation state of macrophages.

Pigs are widely used as animal models in the field of cardiovascular diseases, due to their similarity to the human heart. Therefore, we used porcine macrophages to study the immunomodulatory capacity of secretome from porcine cardiosphere-derived cells (S-CDCs) in vitro.

Porcine macrophages were isolated from the peripheral blood of healthy pigs and polarized to M1 by adding hGM-CSF to the medium. On day 7 of culture, surface receptor expression and cytokine expression were measured by flow cytometry and qPCR in response to 24 hours of LPS + IFNg stimulation and S-CDCs treatment.

M1-polarized macrophages with hGM-CSF and stimulated with LPS + IFNg, and M2-polarized macrophages with hM-CSF and stimulated with IL-4 were used as controls. 

After treatment with S-CDCs, M1 markers such as SLA-II and TNFa decreased whereas M2 markers such as CD206/CD163, Arg-1 and IL-10 increased.

In conclusion, the administration of S-CDCs may have a beneficial effect on the inflammatory phase of AMI.