Myofibroblasts are hybrid cells, combining features of fibroblasts and smooth muscle cells. This dual nature allows them to perform specialized functions, contributing significantly to the body’s natural repair mechanisms following injury. Understanding these cells provides insight into how tissues heal and how these processes can sometimes go awry.
What Are Myofibroblasts?
Myofibroblasts are characterized by their hybrid nature, exhibiting features of both fibroblasts, which produce extracellular matrix components, and smooth muscle cells, which have contractile properties. These cells contain bundles of contractile proteins, such as actin and myosin, forming structures known as stress fibers. Alpha-smooth muscle actin (α-SMA) within these stress fibers serves as a common marker for differentiated myofibroblasts.
The primary source of myofibroblasts in response to injury is the differentiation of local connective tissue fibroblasts. When tissues are damaged, signaling molecules including Transforming Growth Factor-beta (TGF-β), Platelet-Derived Growth Factor (PDGF), and Fibroblast Growth Factor (FGF) trigger this transformation. Other potential origins include smooth muscle cells and epithelial cells undergoing epithelial-mesenchymal transition (EMT). This diverse cellular origin highlights their adaptability.
Myofibroblasts in Healthy Tissue Repair
Myofibroblasts play a constructive role in wound healing. Following tissue damage, these cells migrate to the wound site, attracted by signaling molecules released during inflammation. At the site, myofibroblasts exert contractile forces, pulling the edges of the wound together to reduce its size and promote closure.
Myofibroblasts also synthesize and deposit new extracellular matrix (ECM) components like collagen, fibronectin, and elastin, forming the structural framework for new tissue. This ECM deposition is essential for forming scar tissue, providing mechanical integrity to the injured area. In healthy healing, myofibroblast activity is transient; they disappear through apoptosis once the wound is closed and repaired.
Myofibroblasts in Disease Development
While beneficial in normal wound healing, prolonged or excessive myofibroblast activation leads to pathological conditions, notably fibrotic diseases. In these diseases, myofibroblasts continue to produce and deposit excessive extracellular matrix components, primarily collagen, even after injury resolves. This results in dense, stiff scar tissue, impairing organ function. Examples include liver cirrhosis and idiopathic pulmonary fibrosis.
The persistence of myofibroblasts in fibrotic diseases often stems from their failure to undergo apoptosis, the natural process of cell death that normally occurs after healthy wound repair. This sustained presence contributes to a vicious cycle where fibrosis can promote further fibrosis. Beyond fibrotic diseases, myofibroblasts are also implicated in cancer progression, often called cancer-associated fibroblasts (CAFs). CAFs are abundant in the tumor stroma, contributing to the tumor microenvironment by secreting growth factors and modifying the ECM, which can promote cancer cell proliferation, invasion, and resistance to therapies. The dysregulation of myofibroblast activity represents a significant factor in disease development and progression.