2. Academic Validation
  3. Platelets Facilitate the Wound-Healing Capability of Mesenchymal Stem Cells by Mitochondrial Transfer and Metabolic Reprogramming

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

  • Cell Metab. 2021 Feb 2;33(2):283-299.e9. doi: 10.1016/j.cmet.2020.12.006.
Jennyfer Levoux 1,  Alexandre Prola 2,  Peggy Lafuste 1,  Marianne Gervais 1,  Nathalie Chevallier 3,  Zeynab Koumaiha 1,  Kaouthar Kefi 1,  Laura Braud 1,  Alain Schmitt 4,  Azzedine Yacia 4,  Aurélie Schirmann 1,  Barbara Hersant 5,  Mounia Sid-Ahmed 5,  Sabrina Ben Larbi 6,  Katerina Komrskova 7,  Jakub Rohlena 8,  Frederic Relaix 9,  Jiri Neuzil 10,  Anne-Marie Rodriguez 11
Affiliations

Affiliations

  • 1 Université Paris-Est Créteil, INSERM, IMRB, 94010 Créteil, France.
  • 2 Université Paris-Est Créteil, INSERM, IMRB, 94010 Créteil, France; EnvA, IMRB, 94700 Maisons-Alfort, France.
  • 3 Université Paris-Est Créteil, INSERM, IMRB, 94010 Créteil, France; Etablissement Français du Sang, 94017, Créteil, France.
  • 4 Université de Paris, Institut Cochin, INSERM, CNRS, 75014, Paris, France.
  • 5 Université Paris-Est Créteil, INSERM, IMRB, 94010 Créteil, France; AP-HP, Hôpital Henri Mondor, A. Chenevier, Service de chirurgie plastique et maxillo-faciale, Créteil, France.
  • 6 Institut NeuroMyoGène, Université Claude Bernard - Lyon 1, University Lyon, CNRS UMR 5310, INSERM U1217, Lyon, France.
  • 7 Institute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Prague, Czech Republic; Department of Zoology, Faculty of Science, Charles University, 128 44 Prague 2, Czech Republic.
  • 8 Institute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Prague, Czech Republic.
  • 9 Université Paris-Est Créteil, INSERM, IMRB, 94010 Créteil, France; EnvA, IMRB, 94700 Maisons-Alfort, France; APHP, Hôpitaux Universitaires Henri Mondor & Centre de Référence des Maladies Neuromusculaires GNMH, 94000, Créteil, France.
  • 10 Institute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Prague, Czech Republic; School of Medical Science, Griffith University, Southport, QLD 4222, Australia.
  • 11 Université Paris-Est Créteil, INSERM, IMRB, 94010 Créteil, France. Electronic address: anne-marie.rodriguez@inserm.fr.
PMID: 33400911 DOI: 10.1016/j.cmet.2020.12.006
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.

Keywords

angiogenesis; cell therapy; citrate; de novo; fatty acid synthesis; intercellular mitochondria transfer; mesenchymal stem cells; metabolism reprogramming; mitochondria; mitochondrial respiration; platelets.

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