Altres ajuts: This work was supported by grants from Fundació La Marató de TV3 (201516, 201502), Sociedad Española de Cardiología, Societat Catalana de Cardiologia, [...], and Acadèmia de Ciències Mèdiques i de la Salut de Catalunya i de Balears. [...]. We also appreciate support from the Fundació Privada Daniel Bravo Andreu. Finally, we thank M. Pilar Armengol Barnils from the Microscopic and Genomic Unit of the IGTP, Marta López for her help in fluorescence quantification, and Laura Artigas, from Anaxomics, for her support in secretome analysis.

Mechanical conditioning is incompletely characterized for stimulating therapeutic cells within the physiological range. We sought to unravel the mechanism of action underlying mechanical conditioning of adipose tissue-derived progenitor cells (ATDPCs), both in vitro and in silico. Cardiac ATDPCs, grown on 3 different patterned surfaces, were mechanically stretched for 7 days at 1 Hz. A custom-designed, magnet-based, mechanical stimulator device was developed to apply ~10% mechanical stretching to monolayer cell cultures. Gene and protein analyses were performed for each cell type and condition. Cell supernatants were also collected to analyze secreted proteins and construct an artificial neural network. Gene and protein modulations were different for each surface pattern. After mechanostimulation, cardiac ATDPCs increased the expression of structural genes and there was a rising trend on cardiac transcription factors. Finally, secretome analyses revealed upregulation of proteins associated with both myocardial infarction and cardiac regeneration, such as regulators of the immune response, angiogenesis or cell adhesion. To conclude, mechanical conditioning of cardiac ATDPCs enhanced the expression of early and late cardiac genes in vitro. Additionally, in silico analyses of secreted proteins showed that mechanical stimulation of cardiac ATDPCs was highly associated with myocardial infarction and repair.