Some Historical and Philosophical Reflections on the Myofibroblast Concept

Abstract

The phenomena of wound contraction and scar retraction have been known since the old ages (for review see [29]). In the first part of our century, the work of A. Carrel and P. Lecomte DU NoüY contributed to the notion that the forces producing wound contraction are generated within the granulation tissue itself [5]. These forces were generally considered to depend on extracellular-matrix rearrangements; however, M. Abercrombie and coworkers reported in the 1950s that fibroblasts exert tractional forces in vitro [1]. Similarly, H. Hoffmann-Beerling showed that the addition of adenosine triphosphate (ATP) to permeabilized fibroblasts in culture produces the contraction of their cytoplasm [22]. In this context, and in the context of emerging work on cytoskeleton morphology and function [4], the ultrastructural observation made in our laboratory in 1971 showed that during granulation tissue evolution, fibroblasts acquire smooth-muscle (SM) cell features, such as the presence of cytoplasmic microfilament bundles [17], allowing the proposition that these cells are the source of the force producing wound contraction, and probably connective-tissue retraction during a 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 that are notoriously capable of contracting and relaxing SM cells [18, 28]. 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 of reacting with contraction to a given stimulus by fibroblastic cells depends on their location [18]. The term myofibroblast was suggested for this modified and possibly contractile fibroblast [28].