Adiponectin stimulates exosome release to enhance mesenchymal stem cell driven therapy of heart failure in mice

Mesenchymal stem/stromal cells (MSCs) are cultured adult stem cells originally reside in virtually all tissues and the gain of MSCs by transplantation has become the leading form of cell therapy in various diseases. However, there is limited knowledge on the alteration of its efficacy by factors in recipients. Here we report that the cardioprotective properties of intravenously injected MSCs in a mouse model of pressure-overload heart failure largely depend on circulating adiponectin, an adipocyte secreted factor. The injected MSCs exerted their function through exosomes, extracellular vesicles of endosome-origin. Adiponectin stimulated exosome biogenesis and secretion through binding to T-cadherin, a unique glycosylphosphatidylinositol-anchored cadherin, on MSCs. A pharmacological or adenovirus-mediated genetic increase in plasma adiponectin enhanced the therapeutic efficacy of MSCs. Our findings provide novel insights into the importance of adiponectin in mesenchymal progenitors-mediated organ protections.