Fibroblasts and myofibroblasts in wound healing: Force generation and measurement

Abstract

Fibroblasts are one of the most abundant cell types in connective tissues. These cells are responsible for tissue homeostasis under normal physiological conditions. When tissues are injured, fibroblasts become activated and differentiate into myofibroblasts, which generate large contractions and actively produce extracellular matrix (ECM) proteins to facilitate wound closure. Both fibroblasts and myofibroblasts play a critical role in wound healing by generating traction and contractile forces, respectively, to enhance wound contraction. This review focuses on the mechanisms of force generation in fibroblasts and myofibroblasts and techniques for measuring such cellular forces. Such a topic was chosen specifically because of the dual effects that fibroblasts/myofibroblasts have in wound healing process— a suitable amount of force generation and matrix deposition is beneficial for wound healing; excessive force and matrix production, however, result in tissue scarring and even malfunction of repaired tissues. Therefore, understanding how forces are generated in these cells and knowing exactly how much force they produce may guide the development of optimal protocols for more effective treatment of tissue wounds in clinical settings.

Morphogenesis of 3D vascular networks is regulated by tensile forces

“…VEGF is responsible for initiating vessel formation and inducing molecular and cellular events leading to network stabilization and maturation (39). VEGF inhibition in a coculture of ECs and fibroblasts was predicted to damage the network only whereas the level of forces could be maintained by the fibroblasts (19,40,41). However, the presented results suggest that the force measured during network assembly is applied by both cell types, which provide a synergistic effect on overall force when collaborating to form elongated tubes.…”

Immunohistochemical profile of stromal constituents and lymphoid cells over the course of wound healing in murine model

“…On the other hand, CD20 antigen is an activated-glycosylated . The major source of myofibroblasts in skin wounds is the fibroblasts recruited from dermis and subcutaneous tissues surrounding the wound, but pericytes and vascular smooth muscle cells are also potential able to differentiate into myofibroblasts 15,16 . In this study, the immunohistochemical expression of α-SMA in stromal cells permeating collagen fibers was interpreted as positive markers of myofibroblasts, whereas stained cells surround blood vessels was considered consist with pericytes and then discarded.…”

“…On the other hand, further reduction of myofibroblasts number seems to occur in response to apoptosis mediated by progressive decrease in local levels of TGF-β 16 . Studies have demonstrated that myofibroblasts are essential to wound healing since there is a direct correlation between the wound tension strength, as well as wound contraction rates, and myofibroblasts differentiation 15 . Type I collagen is the major extracellular matrix compound of the dermal and mucosal connective tissues and it is fundamental to ensure the optimal mechanical properties of the healing scar.…”

Ankaferd-Induced Early Soft Tissue Wound Healing in an Experimental Rat Model

“…28 Additionally it is known that, contraction of fibroblasts in certain connective tissues plays a critical role in the closure of skin wounds during healing. [29][30][31][32] Statistically significant increase of α-SMA in ABS group represents an accelerating action for wound healing, reflecting increased tissue contraction which results in decreased area of the wound. ABS effect over α-SMA separately may be the most important point for ABS' mode of action in accelerating the wound healing rate by decreasing the wound area.…”