Objectives The poor survival of cells in ischaemic myocardium is a major obstacle for stem cell therapy. Exendin-4 holds the potential of cardio protective effect based on their pleiotropicactivity. This study investigated whether Exendin-4 in conjunction with adipose derived stem cells (ADSCs) could improve the stem cells survival and contribute to myocardial repair after myocardial infarction.
Methods MI was induced by the left anterior descending artery ligation in adult male Sprague-Dawley rats. ADSCs carrying double-fusion reporter gene (fire flyluciferase and monomeric red fluorescent protein (fluc-mRFP)) were quickly injected into border zone of myocardial infarction in rats treated with or without Exendin-4.
Results Longitudinal in vivo bioluminescence imaging indicated that Exendin-4 enhanced the survival of transplanted ADSCs. Moreover, ADSCs adjuvant with Exendin-4 decreased oxidativestress, apoptosis and fibrosis, improved myocardial viability and cardiac function, as well as increased the differentiation rates of ADSCs into cardiomyocyte sand vascular smooth muscle cells in vivo. Then, ADSCs were exposed to hydrogen peroxide/serum deprivation (H2O2/SD) to mimic the ischaemic environment in vitro. Exendin-4 decreased the apoptosis and enhanced the paracrine effect of ADSCs. Western blotting demonstrated that Exendin-4 activated STAT3 through the phosphorylation of Akt and ERK1/2. Furthermore, Exendin-4 increased theanti-apoptotic protein Bcl-2 and decreased the pro-apoptotic protein Bax of ADSCs.
Conclusions Exendin-4 could improve the survival and therapeutic efficacy of transplanted ADSCs through STAT3 activation via the phosphorylation of Akt and ERK1/2. This study suggests the potential of Exendin-4 for stem cell based heart regeneration.