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

J. Levoux, A. Prola, P. Lafuste, M. Gervais, N. Chevallier, Z. Koumaiha, K. Kefi, L. Braud, A. Schmitt, A. Yacia, A. Schirmann, B. Hersant, M. Sid-Ahmed, S. Ben Larbi, K. Komrskova, J. Rohlena, F. Relaix, J. Neuzil, AM. Rodriguez

. 2021 ; 33 (2) : 283-299.e9. [pub] 20210104

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22004630

Grantová podpora
NV17-30138A MZ0 CEP - Centrální evidence projektů

Digitální knihovna NLK
Plný text - Článek

E-zdroje Online Plný text

NLK Cell Press Free Archives od 2005-01-01 do Před 1 rokem
Free Medical Journals od 2005 do Před 1 rokem

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.

Citace poskytuje Crossref.org

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