Mayrand D, Laforce-Lavoie A, Larochelle S, Langlois A, Genest H, Roy M, Moulin VJ, et al.
Angiogenesis. Date of publication 2012 Jun 1;volume 15(2):199-212.
1. Angiogenesis. 2012 Jun;15(2):199-212. doi: 10.1007/s10456-012-9253-5. Epub 2012
Feb 18.
Angiogenic properties of myofibroblasts isolated from normal human skin wounds.
Mayrand D(1), Laforce-Lavoie A, Larochelle S, Langlois A, Genest H, Roy M, Moulin
VJ.
Author information:
(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, Université Laval, Québec, QC, Canada.
Comment in
Regen Med. 2012 May;7(3):275-7.
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.
DOI: 10.1007/s10456-012-9253-5
PMID: 22350743 [Indexed for MEDLINE]