Platelets Facilitate the Wound-Healing Capability of Mesenchymal Stem Cells by Mitochondrial Transfer and Metabolic Reprogramming - Archive ouverte HAL Access content directly
Journal Articles Cell Metabolism Year : 2021

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

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Peggy Lafuste
Marianne Gervais
Alain Schmitt
  • Function : Author
Azzedine Yacia
  • Function : Author
Jakub Rohlena

Abstract

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

Dates and versions

inserm-03163419 , version 1 (09-03-2021)

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Cite

Jennyfer Levoux, Alexandre Prola, Peggy Lafuste, Marianne Gervais, Nathalie Chevallier, et al.. Platelets Facilitate the Wound-Healing Capability of Mesenchymal Stem Cells by Mitochondrial Transfer and Metabolic Reprogramming. Cell Metabolism, 2021, 33 (2), pp.283-299.e9. ⟨10.1016/j.cmet.2020.12.006⟩. ⟨inserm-03163419⟩
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