Myofibroblast

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A myofibroblast is a cell phenotype that was first described as being in a state between a fibroblast and a smooth muscle cell.

Structure

Myofibroblasts are contractile web-like fusiform cells that are identifiable by their expression of α-smooth muscle actin within their cytoplasmic stress fibers.^[1]

In the gastrointestinal and genitourinary tracts, myofibroblasts are found subepithelially in mucosal surfaces. Here they not only act as a regulator of the shape of the crypts and villi, but also act as stem-niche cells in the

Location

Myofibroblasts were first identified in granulation tissue during skin wound healing.^[2] Typically, these cells are found in granulation tissue, scar tissue (fibrosis) and the stroma of tumours. They also line the gastrointestinal tract, wherein they regulate the shapes of crypts and villi.

Markers

Myofibroblasts usually stain for the intermediate filament

Myofibroblasts upregulate the expression of fibronectin, collagens, and hyaluronic acid during and after their differentiation from fibroblasts. Among these, the EDA isoform of fibronectin (EDA-FN), and collagen type I (COL1A1/COL1A2) are typical markers of myofibroblast-dependent synthesis of pro-fibrotic extracellular matrix.

Some myofibroblasts (especially if they have a stellate form) may also be positive for GFAP.

Development

There are many possible ways of myofibroblast development:

1. Partial smooth muscle differentiation of a fibroblastic cell
2. Activation of a stellate cell (e.g.
   pancreatic stellate cells
   ).
3. Loss of contractile phenotype (or acquisition of "synthetic phenotype") of a smooth muscle cell.
4. Direct myofibroblastic differentiation of a progenitor cell resident in a stromal tissue.
5. Homing and recruitment of a circulating mesenchymal precursor which can directly differentiate as above or indirectly differentiate through the other cell types as intermediates.
6. Epithelial to mesenchymal transdifferentiation (
   epithelial cell
   .

Perhaps the most studied pathway of myofibroblast formation is

Function

In many organs like liver, lung, and kidneys, they are primarily involved in fibrosis. In the wound tissue they are implicated in wound strengthening by extracellular collagen fiber deposition and then wound contraction by intracellular contraction and concomitant alignment of the collagen fibers by integrin-mediated pulling on to the collagen bundles.

Myofibroblasts can contract by using smooth muscle type actin-myosin complex, rich in a form of actin called alpha-smooth muscle actin. These cells are then capable of speeding wound repair by contracting the edges of the wound.

Early work on wound healing showed that granulation tissue taken from a wound could contract in vitro (or in an organ bath) in a similar fashion to smooth muscle, when exposed to substances that cause smooth muscle to contract, such as adrenaline or angiotensin.

More recently it has been shown that fibroblasts can transform into myofibroblasts with

After healing is complete, these cells are lost through

• List of human cell types derived from the germ layers

References