Evolution and clinical implications of the myofibroblast concept

Time for primary review 21 days. The phenomena of wound contraction and scar retraction are known since old ages (for review see 1). In the first part of our century, the work of Carrel and Lecomte du Nouy has contributed to the notion that the forces producing wound contraction are generated within the granulation tissue itself 2. These forces were generally considered to depend on extracellular matrix rearrangements; however, Abercrombie and co-workers reported, in the fifties, that fibroblasts exert tractional forces in vitro 3. Similarly, Hoffmann-Beerling showed that addition of ATP to permeabilized fibroblasts in culture produces a contraction of their cytoplasm 4. In this context, and in the context of emerging work on cytoskeleton morphology and function 5, the ultrastructural observation made in our laboratory in 1971 that during granulation tissue evolution fibroblasts acquire smooth muscle (SM) cell features, such as the presence of cytoplasmic microfilament bundles 6, lead to the proposition that these cells are the source of the force producing wound contraction, and probably connective tissue retraction during fibrotic phenomena. Shortly thereafter, it was shown that strips of granulation tissue isolated and placed in a pharmacological bath would contract and relax under the influence of substances which are known to be capable of contracting and relaxing SM cells 7, 8. It is noteworthy (particularly because this observation has never been developed) that granulation tissues from different locations respond differently to the same agonist or antagonist stimulus, suggesting that the capacity to react with contraction to a given stimulus by fibroblastic cells depends on their location 8. The name myofibroblast was suggested for this modified and possibly contractile fibroblast 7. During the next few years, several laboratories reported by means of ultrastructural techniques the presence of myofibroblasts in several lesions … * Corresponding author. Tel.: +41 (22) 702–5742; Fax: +41 (22) 702–5746; E-mail: giulio.gabbiani@medecine.unige.ch