Myofibroblast

  A Myofibroblast is a cell that is in between a fibroblast and a smooth muscle cell in differentiation.

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Developmental origin

There are many possible ways of myofibroblast development:

1. Partial smooth muscle differentiation of a fibroblastic cell
2. Activation of a stellate cell (eg Hepatic Ito cells or 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 of an epithelial cell.

Markers

Myofibroblasts usually stain for the intermediate filament vimentin which is a general mesenchymal marker and "alpha smooth muscle actin". They are positive for other smooth markers like another intermediate filament type desmin positive in some tissues but may be negative for desmin in some others. Similar heterogeneous positivity may exist for almost every smooth muscle marker except probably a few which are positive only in contractile smooth muscles like metavinculin and smoothelin. Some myofibroblasts (esp if they have a stellate form) may also be positive for GFAP.

Location and function

Myofibroblasts are found subepithelially in many mucosal surfaces for example almost throughout whole of the gastrointestinal tract and the genitourinary tract. 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 intestinal crypts and as parts of atypical antigen presenting cells. They have both support as well as paracrine function in most places. In many organs like liver lung and kidney 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. Pericytes and renal mesangial cells are some examples of modified myofibroblast like cells.

Myofibroblasts in wound healing

It can contract by using smooth muscle type actin-myocin 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 photobiomodulation.

After healing is complete, these cells are lost through apoptosis and it has been suggested that in several fibrotic diseases (for example liver cirrhosis, kidney fibrosis, retroperitoneal fibrosis) that this mechanism fails to work, leading to persistence of the myofibroblasts, and consequently expansion of the extracellular matrix (fibrosis) and contraction.

Similarly, in wounds that fail to resolve and become keloids or hypertrophic scars, myofibroblasts may persist, rather than disappearing by apoptosis.