Platelets Facilitate the Wound-Healing Capability of Mesenchymal Stem Cells by Mitochondrial Transfer and Metabolic Reprogramming
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
33400911
DOI
10.1016/j.cmet.2020.12.006
PII: S1550-4131(20)30661-6
Knihovny.cz E-resources
- Keywords
- angiogenesis, cell therapy, citrate, de novo, fatty acid synthesis, intercellular mitochondria transfer, mesenchymal stem cells, metabolism reprogramming, mitochondria, mitochondrial respiration, platelets,
- MeSH
- Wound Healing MeSH
- Mesenchymal Stem Cells metabolism MeSH
- Mitochondria metabolism MeSH
- Mice, Inbred C57BL MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Blood Platelets metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
Institute of Biotechnology Czech Academy of Sciences 252 50 Prague West Prague Czech Republic
Université de Paris Institut Cochin INSERM CNRS 75014 Paris France
Université Paris Est Créteil INSERM IMRB 94010 Créteil France
Université Paris Est Créteil INSERM IMRB 94010 Créteil France; EnvA IMRB 94700 Maisons Alfort France
References provided by Crossref.org
Functional mitochondrial respiration is essential for glioblastoma tumour growth
Recommendations for mitochondria transfer and transplantation nomenclature and characterization
Mitochondria on the move: Horizontal mitochondrial transfer in disease and health
