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Angiogenic properties of myofibroblasts isolated from normal human skin wounds

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Abstract

During wound healing, angiogenesis plays a crucial role in inducing adequate perfusion of the new tissue, thereby allowing its survival. This angiogenic process contributes to the formation of granulation tissue, alongside myofibroblasts. Myofibroblasts are cells specialized in wound contraction and synthesis of new extracellular matrix. Fibroblasts, considered by some to be at the origin of myofibroblasts, have already been shown to promote neovascularization. Thus, we hypothesized that myofibroblasts play a key role during angiogenic development in wound healing. We isolated myofibroblasts from normal human skin wounds and dermal microvascular endothelial cells (HDMVEC) and fibroblasts from skin. Using an in vitro fibrin-based model, we compared the proangiogenic activity of wound myofibroblasts to that of fibroblasts in the presence of HDMVEC. By immunostaining with collagen IV antibodies, we observed the formation of a capillary network significantly more developed when HDMVEC were cultured with myofibroblasts compared to the network formed in the presence of fibroblasts. The differences between these cell types did not result from a differential secretion of Vascular Endothelial Growth Factor or basic Fibroblast Growth Factor. However, in the presence of myofibroblasts, a significant decrease in matrix metalloproteinase activity was observed. This finding was correlated with a significant increase in Tissue Inhibitor of MetalloProteinase (TIMP)-1 and TIMP-3. Furthermore, inhibition of TIMP-1 secretion using shRNA significantly decreased myofibroblasts induced angiogenesis. These results led to the hypothesis that normal wound myofibroblasts contribute to the vascular network development during wound healing. Our data emphasize the critical role of wound myofibroblasts during healing.

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Acknowledgments

The authors would like to acknowledge the Canadian Institutes of Health Research, Fondation du CHA-Hôpital Enfant-Jesus/Saint-Sacrement and Thecell network. The authors also want to thank Benoît Cordier and Samuel Blanchette for technical assistance. V. M. was the recipient of a scholarship from Fonds de la Recherche en Santé du Québec.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Centre LOEX de l’Université Laval, Génie tissulaire et régénération: LOEX du Centre de Recherche FRSQ du Centre Hospitalier Affilié Universitaire de Québec, Département de Chirurgie, Faculté de Médecine, Université Laval, Québec, QC, Canada

    Dominique Mayrand, Audrey Laforce-Lavoie, Sébastien Larochelle, Amélie Langlois & Véronique J. Moulin

  2. Centre Hospitalier Affilié Universitaire de Québec, Québec, QC, Canada

    Hervé Genest & Michel Roy

  3. LOEX, Hôpital de l’Enfant-Jésus, 1401, 18e rue, Québec, QC, G1J 1Z4, Canada

    Véronique J. Moulin

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  1. Dominique Mayrand
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Correspondence to Véronique J. Moulin.

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Mayrand, D., Laforce-Lavoie, A., Larochelle, S. et al. Angiogenic properties of myofibroblasts isolated from normal human skin wounds. Angiogenesis 15, 199–212 (2012). https://doi.org/10.1007/s10456-012-9253-5

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