Molecular regulation of myofibroblast formation

Novel strategies are required to counteract tissue contractures characteristic for organ fibrosis, stroma reaction to tumors, host reaction to implants, and formation of hypertrophic scars as after burns. Key element for the development and progression of these pathologies is the excessive contractile force generated by a-smooth muscle actin (a-SMA)-expressing myofibroblasts. We can modulate myofibroblast tension using multiple techniques, including collagen gels of different stiffness, novel substrates with tunable compliance, stretchable culture membranes and cell shape restriction by microcontact-printing. On the molecular level, we specifically interfere with the contractile apparatus, matrix-adhesion, cell-adhesion and growth factor activation of myofibroblasts. In general, stress-release leads to de-differentiation and ⁄or apoptosis of myofibroblasts. We propose therapeutically interfering with their stress-perception and -transmission apparatus as innovative strategy to eliminate fibrogenic cells.