Yuto Nakamura 1 , Shunbun Kita 1 , 2 , ∗ , Yoshimitsu Tanaka 1 , Shiro Fukuda 1 , Yoshinari Obata 1 , Tomonori Okita 1 , Hiroyuki Nishida 3 , 4 , Yuki Takahashi 5 , Yusuke Kawachi 1 , Yuri Tsugawa-Shimizu 1 , Yuya Fujishima 1 , Hitoshi Nishizawa 1 , Yoshinobu Takakura 5 , Shigeru Miyagawa 6 , Yoshiki Sawa 6 , 7 , Norikazu Maeda 1 , 8 , Iichiro Shimomura 1
10 July 2020
Mesenchymal stem/stromal cells (MSCs) are cultured adult stem cells that 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 exert 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-progenitor-mediated organ protections.
Mesenchymal stem/stromal cell (MSC) therapies are emergently under development for various diseases such as heart failure and also acute respiratory distress syndrome (ARDS) evoked by COVID-19 infections. Nakamura et al. uncovered the importance of adiponectin in the circulation and T-cadherin in human adipose-derived MSCs to enhance exosome synthesis reading to treat a heart failure model.