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

0542170 - BTÚ 2022 RIV US eng J - Journal Article
Levoux, J. - Prola, A. - Lafuste, P. - Gervais, M. - Chevallier, N. - Koumaiha, Z. - Kefi, K. - Braud, L. - Schmitt, A. - Yacia, A. - Schirmann, A. - Hersant, B. - Sid-Ahmed, M. - Ben Larbi, S. - Komrsková, Kateřina - Rohlena, Jakub - Relaix, F. - Neužil, Jiří - Rodriguez, A.-M.
Platelets Facilitate the Wound-Healing Capability of Mesenchymal Stem Cells by Mitochondrial Transfer and Metabolic Reprogramming.
Cell Metabolism. Roč. 33, č. 2 (2021), s. 283-299. ISSN 1550-4131. E-ISSN 1932-7420
R&D Projects: GA ČR(CZ) GA20-18513S; GA ČR(CZ) GA18-10832S; GA ČR(CZ) GA20-05942S; GA MZd(CZ) NU20-03-00309; GA MZd(CZ) NV17-30138A
Institutional support: RVO:86652036
Keywords : angiogenesis * cell therapy * de novo * fatty acid synthesis * citrate
OECD category: Cell biology
Impact factor: 31.373, year: 2021
Method of publishing: Open access
https://www.sciencedirect.com/science/article/abs/pii/S1550413120306616?via%3Dihub

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.
Permanent Link: http://hdl.handle.net/11104/0319655