Endocrine Abstracts

The functional oxytocin (OT) system is present in the heart and stimulate cardiomyocyte (CM) differentiation of embryonic stem cells. Presently, we are reporting that the OT stimulates CM differentiation of stem cells isolated from the rat heart and termed as side population cells (SP). Specifically, the phenotype of SP-CD31(−) cells, but not SP-CD31(+) cells, proliferate in the presence of OT; the OT treatment promote cell aggregation, and then stimulate differentiation into beating cell colonies. These colonies of contractile cells express the markers of a CMs phenotype such as troponin, MLC2V and actinin. Moreover, SP cells stimulated by OT produce endothelial phenotype in the Matrigel culture. Among adult stem cells, mesenchymal stem cells (MSCs) possess unique properties that make them eligible for convenient and highly effective cell therapy of the heart. The rat bone marrow MSCs preconditioned with the OT present a rapid increase and nuclear accumulation of phospho-Akt and of phospho-p44/42 (ERK1/2), indicating an activation of the protective way phosphatidylinositol-3-kinase (PI3K)/AKT and mitogen-activated protein kinases (MAPK) respectively. MSCs carrying OT gene stimulate angiogenesis ex vivo and in vivo in rat model of hind-limb ischemia. The preconditioning to the OT increases the metabolic activity of the MSCs cells in normoxia, stimulation of cellular trafficking of GLUT 4 transporter and seems to protect against the hypoxia and the serum deprivation as evaluated by the MTT test. As demonstrated by flow cytometry for annexin V and Tunel method, the OT preconditioning reduced apoptosis in rat MSCs exposed to hypoxia. This anti-apoptotic protection was transmitted from MSCs to CMs in co-culture. In conclusion, we propose that stem cells optimized by OT treatment may play the supportive role in injured heart via differentiation to cardiac cells and secretion of paracrine factors.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.