Angiogenic properties of myofibroblasts isolated from normal human skin wounds

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.

α‐2‐Macroglobulin induces the shedding of microvesicles from cutaneous wound myofibroblasts

“…Throughout this second phase of the healing process, dermal fibroblasts are recruited to the site of injury, where they proliferate and undergo differentiation into contractile myofibroblasts (Wmyos; Gabbiani, Ryan, & Majne, ). Wmyos actively contribute to the development of granulation tissue by synthetizing temporary extracellular matrix components and promoting angiogenesis (Mayrand et al, ; V. Moulin et al, ). Wound healing concludes with matrix remodeling and neovessel regression, resulting in the transformation of granulation tissue into mature scar tissue (Desmouliere, Redard, Darby, & Gabbiani, ).…”

Bone mesenchymal stem cells differentiate into myofibroblasts in the tumor microenvironment

“…Currently, it is generally accepted that myofibroblasts possess similar features to fibroblasts and smooth muscle cells, as they express the fibroblast marker vimentin and the smooth muscle marker α-SMA (23). Myofibroblasts have roles in contraction, secretion and synthesis, and possess a significant role in injury healing, organogenesis and tissue molding (24,25).…”

The physiology of wound healing

“…Myofibroblasts also promote angiogenesis through mediation MMP activity. 10 Collagens synthesized by fibroblasts are the key component in providing strength to tissues. In wounds closed by primary intention, collagen deposition is maximal by day 5 and this can often be palpated beneath the skin as a 'wound ridge'.…”