Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Adipose Management, Graduate School of Medicine, Osaka University, Osaka, Japan.
Mol Ther. 2020 Oct 7;28(10):2203-2219. doi: 10.1016/j.ymthe.2020.06.026. Epub 2020 Jul 10.
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.
间充质干细胞（MSCs）是一种培养的成体干细胞，最初存在于几乎所有组织中，通过移植获得 MSCs 已成为各种疾病中细胞治疗的主要形式。然而，对于受体中因素对其疗效的改变知之甚少。在这里，我们报告说，静脉注射的 MSCs 在压力超负荷性心力衰竭的小鼠模型中的心脏保护特性在很大程度上取决于循环脂联素，这是一种脂肪细胞分泌的因子。注射的 MSCs 通过外泌体发挥其功能，外泌体是内体来源的细胞外囊泡。脂联素通过与 T-钙粘蛋白（MSC 上独特的糖基磷脂酰肌醇锚定钙粘蛋白）结合来刺激外泌体的生物发生和分泌。药理学或腺病毒介导的血浆脂联素的基因增加增强了 MSCs 的治疗效果。我们的研究结果为脂联素在间充质祖细胞介导的器官保护中的重要性提供了新的见解。
