Fig. 8. Schematic diagram of the enhanced effects of MSCs on myocardial repair induced by CTRP3 overexpression.

Genetic manipulation of CTRP3 in MSCs restores CTRP3 levels. In vivo, overexpression of CTRP3 improves survival/retention of transplanted MSCs in ischemic microenvironment and enhances the therapeutic effect of MSCs on MI, however, knocking down CTRP3 impairs therapeutic efficacy of MSCs. Further, there is a positive feedback loop between MSCs and CTRP3. CTRP3 activates the ERK1/2-MMP9 pathway to promote proliferation and migration and the ERK1/2-Mt1/2/Sod2 pathway to improve survival, the latter of which resists oxidative stress and in turn upregulates CTRP3 expression. The released CTRP3 increases the retention/survival of MSCs in infarcted heart. In addition, CTRP3 inhibits myocardial apoptosis and induces the expression of the angiogenic factor VEGF as reported previously by us. CTRP3 overexpression in MSCs may be a novel therapeutic strategy that benefits both MSCs and cardiomyocytes and potentiates the curative effects of MSCs after MI