Cell therapy constitutes a promising strategy for the treatment of myocardial infarction. To better control the survival, the differentiation and the integration of the grafted cells, we have used a tissue-engineering approach associating the cells with a microvector comprising a biomimetic surface and able to release a growth factor (GF), the pharmacologically active microcarriers (PAM). Among the cell used for such approach, adipose-derived stem cells (ADSC) do not raise ethical concerns/issues and allow autologous transplantation. These cells are widely studied for the regeneration of various tissues due to their immunoregulatory properties, their potential to secrete GFs and chemokines but also their large potential of differentiation. In a first step, we have investigated the effect of extracellular matrix molecules and PAMs on ADSCs differentiation into cardiomyocytes in combination with a GF cocktail. We have thus observed that the GFs cocktail allowed cell commitment into the cardiac lineage after 2 weeks. Comparing the effects of the laminin (LM) and fibronectin (FN) on this differentiation, we found that LM allowed ADSCs differentiation into a more mature phenotype. Moreover, the enrichment of the GF cocktail with TGF!1 potentiated the LM effect. Finally, providing PAM covered with LM allowed an earlier differentiation into cardiac lineage in combination with the cocktail. PAMs can release a GF in a prolonged manner. Consequently, we encapsulated 3 proteins, the VEGF, the HGF and the IGF-1, and assessed their effect on ADSCs behavior. We observed that PAMs releasing HGF and IGF-1 induced ADSCs cardiomyogenic differentiation. Moreover, we also observed ADSCs cardiac differentiation markers expression, when ADSCPAMs complexes are integrated within a thermosensitive hydrogel. However, we also found that the amount of protein released from PAMs decreased within the gel. In a last part we have sought to improve protein release profile from PAMs changing polymer composition. So, we used various triblock copolymers of PLGA-PEG-PLGA to formulate microspheres and then evaluated their role on protein release but also on protein stability during polymer degradation.
