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Platelets Promote Pro-Angiogenic Activity of Mesenchymal Stem Cells Via Mitochondrial Transfer and Metabolic Reprogramming

41 Pages Posted: 3 Mar 2020 Publication Status: Published

See all articles by Jennyfer Levoux

Jennyfer Levoux

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

Alexandre Prola

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

Peggy Lafuste

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

Marianne Gervais

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

Laura Braud

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

Aurélie Schirmann

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

Barbara Hersant

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

Mounia Sid-Ahmed

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

Sabrina Ben-Larbi

University of Claude Bernard Lyon 1 - Institut NeuroMyoGène

Katerina Komrskova

Czech Academy of Sciences - Institute of Biotechnology

Jakub Rohlena

Czech Academy of Sciences - Institute of Biotechnology

Frederic Relaix

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

Jiri Neuzil

Czech Academy of Sciences - Institute of Biotechnology

Anne-Marie Rodriguez

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

More...

Abstract

Platelets are known to enhance the wound-healing activity of mesenchymal stem cells (MSCs). However, the mechanism by which platelets improve MSC therapeutic potential has not been elucidated. Here we provide evidence that, upon their activation, platelets transfer respiratory-competent mitochondria to MSCs. We found that this process boosts the therapeutic efficacy of MSCs following their engraftment in a mouse wound healing injury model. By combining in vitro and in vivo experiments, we demonstrated that platelet-derived mitochondria promote the pro-angiogenic activity of MSCs through their metabolic remodeling. Notably, we show that activation of the de novo fatty acid synthesis pathway is required for the increased secretion of pro-angiogenic factors by platelet-preconditioned MSCs. These results reveal a new mechanism by which platelets potentiate properties of MSCs throughout mitochondria transfer and metabolic conversion of MSCs.

Keywords: Mesenchymal stem cells, Mitochondria, Platelets, Metabolism reprogramming, Angiogenesis, De novo fatty acid synthesis

Suggested Citation

Levoux, Jennyfer and Prola, Alexandre and Lafuste, Peggy and Gervais, Marianne and Braud, Laura and Schirmann, Aurélie and Hersant, Barbara and Sid-Ahmed, Mounia and Ben-Larbi, Sabrina and Komrskova, Katerina and Rohlena, Jakub and Relaix, Frederic and Neuzil, Jiri and Rodriguez, Anne-Marie, Platelets Promote Pro-Angiogenic Activity of Mesenchymal Stem Cells Via Mitochondrial Transfer and Metabolic Reprogramming. Available at SSRN: https://ssrn.com/abstract=3545511 or http://dx.doi.org/10.2139/ssrn.3545511
This version of the paper has not been formally peer reviewed.

Jennyfer Levoux

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

France

Alexandre Prola

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

France

Peggy Lafuste

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

France

Marianne Gervais

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

France

Laura Braud

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

France

Aurélie Schirmann

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

France

Barbara Hersant

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB) ( email )

France

Mounia Sid-Ahmed

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB) ( email )

France

Sabrina Ben-Larbi

University of Claude Bernard Lyon 1 - Institut NeuroMyoGène ( email )

Lyon
France

Katerina Komrskova

Czech Academy of Sciences - Institute of Biotechnology

Czech Republic

Jakub Rohlena

Czech Academy of Sciences - Institute of Biotechnology

Czech Republic

Frederic Relaix

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB) ( email )

France

Jiri Neuzil

Czech Academy of Sciences - Institute of Biotechnology ( email )

Czech Republic

Anne-Marie Rodriguez (Contact Author)

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB) ( email )

France

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