法国巴黎埃斯特·克雷泰伊大学Anne-Marie Rodriguez研究组近日取得一项新成果。他们揭示血小板通过线粒体转移和代谢重编程促进间充质干细胞（MSC）的伤口愈合能力。相关论文发表在2021年1月4日出版的《细胞-代谢》上。

他们提供的证据表明，血小板被激活后，主要通过动力蛋白依赖性网格蛋白介导的内吞作用，将具有呼吸功能的线粒体转移至MSC。他们发现，此过程增强了MSCs植入多种组织损伤小鼠模型（包括全层皮肤伤口和营养不良的骨骼肌）后的治疗效果。通过结合体外和体内实验，他们证明了血小板源性线粒体通过其代谢重塑促进了MSC的促血管生成活性。

值得注意的是，他们显示了血小板预处理的MSC增加从头脂肪酸合成途径的激活，这是促血管生成因子分泌增加所必需的。这些结果揭示了血小板增强MSC特性的新机制，并强调了在临床使用前测试血小板线粒体质量的重要性。

研究人员表示，已知血小板可增强MSC的伤口愈合活性。然而，尚未阐明血小板改善MSC的治疗潜力的机制。

附：英文原文

Title: Platelets Facilitate the Wound-Healing Capability of Mesenchymal Stem Cells by Mitochondrial Transfer and Metabolic Reprogramming

Author: Jennyfer Levoux, Alexandre Prola, Peggy Lafuste, Marianne Gervais, Nathalie Chevallier, Zeynab Koumaiha, Kaouthar Kefi, Laura Braud, Alain Schmitt, Azzedine Yacia, Aurélie Schirmann, Barbara Hersant, Mounia Sid-Ahmed, Sabrina Ben Larbi, Katerina Komrskova, Jakub Rohlena, Frederic Relaix, Jiri Neuzil, Anne-Marie Rodriguez

Issue&Volume: 2021-01-04

Abstract: Platelets are known to enhance the wound-healing activity of mesenchymal stem cells(MSCs). However, the mechanism by which platelets improve the therapeutic potentialof MSCs has not been elucidated. Here, we provide evidence that, upon their activation,platelets transfer respiratory-competent mitochondria to MSCs primarily via dynamin-dependentclathrin-mediated endocytosis. We found that this process enhances the therapeuticefficacy of MSCs following their engraftment in several mouse models of tissue injury,including full-thickness cutaneous wound and dystrophic skeletal muscle. By combiningin vitro and in vivo experiments, we demonstrate that platelet-derived mitochondria promote the pro-angiogenicactivity of MSCs via their metabolic remodeling. Notably, we show that activationof the de novo fatty acid synthesis pathway is required for increased secretion of pro-angiogenicfactors by platelet-preconditioned MSCs. These results reveal a new mechanism by whichplatelets potentiate MSC properties and underline the importance of testing plateletmitochondria quality prior to their clinical use.

DOI: 10.1016/j.cmet.2020.12.006

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30661-6