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Pro-angiogenic capacities of microvesicles produced by skin wound myofibroblasts

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Abstract

Wound healing is a very highly organized process where numerous cell types are tightly regulated to restore injured tissue. Myofibroblasts are cells that produce new extracellular matrix and contract wound edges. We previously reported that the human myofibroblasts isolated from normal wound (WMyos) produced microvesicles (MVs) in the presence of the serum. In this study, MVs were further characterized using a proteomic strategy and potential functions of the MVs were determined. MV proteins isolated from six WMyo populations were separated using two-dimensional differential gel electrophoresis. Highly conserved spots were selected and analyzed using mass spectrometry resulting in the identification of 381 different human proteins. Using the DAVID database, clusters of proteins involved in cell motion, apoptosis and adhesion, but also in extracellular matrix production (21 proteins, enrichment score: 3.32) and in blood vessel development/angiogenesis (19 proteins, enrichment score: 2.66) were identified. Another analysis using the functional enrichment analysis tool FunRich was consistent with these results. While the action of the myofibroblasts on extracellular matrix formation is well known, their angiogenic potential is less studied. To further characterize the angiogenic activity of the MVs, they were added to cultured microvascular endothelial cells to evaluate their influence on cell growth and migration using scratch test and capillary-like structure formation in Matrigel®. The addition of a MV-enriched preparation significantly increased endothelial cell growth, migration and capillary formation compared with controls. The release of microvesicles by the wound myofibroblasts brings new perspectives to the field of communication between cells during the normal healing process.

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Acknowledgements

This work was supported by Natural Sciences and Engineering Research Council of Canada (NSERC) (RGPIN-2014-04404); Le Réseau de Thérapie Cellulaire et Tissulaire du FRQS (ThéCell). MM was recipient of a Soeurs Mallet fellowship.

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  1. Mays Merjaneh and Amélie Langlois have contributed equally to this work.

Authors and Affiliations

  1. Centre de recherche en organogenese experimentale de l’Université Laval/LOEX, Centre de recherche du CHU de Quebec and Surgery Department, Faculty of Medicine, Universite Laval, 1401, 18e rue, Quebec City, QC, G1J 1Z4, Canada

    Mays Merjaneh, Amélie Langlois, Sébastien Larochelle & Véronique J. Moulin

  2. CHU de Québec, Quebec City, QC, Canada

    Chanel Beaudoin Cloutier

  3. Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), UMR 5246 Université Lyon 1, CNRS, INSA Lyon, CPE Lyon, Villeurbanne, France

    Sylvie Ricard-Blum

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  1. Mays Merjaneh
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Correspondence to Véronique J. Moulin.

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Merjaneh, M., Langlois, A., Larochelle, S. et al. Pro-angiogenic capacities of microvesicles produced by skin wound myofibroblasts. Angiogenesis 20, 385–398 (2017). https://doi.org/10.1007/s10456-017-9554-9

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  • DOI: https://doi.org/10.1007/s10456-017-9554-9

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