Mesenchymal stem cells rejuvenate cardiac muscle after ischemic injury.

Previous studies have shown that transplantation of mesenchymal stem cells (MSCs) enhances myocardial regeneration after myocardial infarction (MI), primarily resulting from the production and release of trophic growth factors and cytokines by MSCs. However, effects of MSCs or a subtype of MSCs on the ageing of injured cardiac muscle cells (CMCs) are limitedly known. Here, we addressed this question. CD146+ MSCs were isolated from total MSCs (tMSCs), and their effects on injured CMCs were assessed. In vivo, transplantation of isogenic CD146+ MSCs into MI-mice increased the proliferation of CMCs and reduced apoptosis of CMCs in a significantly higher degree than transplantation of tMSCs, resulting in significant improvement of the heart function. In vitro, CMCs were co-cultured under hypoxia condition with CD146+MSCs or tMSCs. We found that CD146+MSCs increased the proliferation of CMCs and reduced apoptosis of CMCs in a significantly higher degree, compared to tMSCs, likely resulting from reduction of aging-associated cellular reactive oxygen species in CMCs. Together, these data suggest that MSCs rejuvenate CMCs after ischemic injury and a subtype of MSCs, CD146+ MSCs, appears to have higher potential in coordinating this process.