New hypothesis concerning pathogenesis of systemic sclerosis using a tissue engineering method

Abstract

Scleroderma is a connective tissue disease characterized by skin and internal organs fibrosis, vasculopathy of small arteries and activation of the immune system. The objective of this project is to study the capacity of scleroderma fibroblasts to induce fibrosis using a model of tissue engineered dermis. Fibroblasts were isolated from skin biopsies of patient with scleroderma for less than one year (early stage) or for more than ten years (late stage). For each patient, two biopsies were taken, one from affected area and the other one from a non‐affected area. Control fibroblasts were obtained from healthy donors. Only fibroblasts isolated from the skin biopsies from affected area of patient at late stage of scleroderma were able to reconstruct dermis thicker than that obtained with control fibroblasts. All of the other fibroblasts tested formed dermis thinner than the one obtained with control fibroblasts. These observations are not the consequence of a change in the amount of fibroblast present, but due to a different turnover of extracellular matrix (matrix metalloproteinase‐1/collagen I) according to the stage and the area. These results suggest the necessary presence of exogenous factor(s) to induce fibrosis in the early stage of the disease, while in late stage these factor(s) would not be essential. This study was supported by CIHR, by the “Fondation de l’Hôpital St‐Sacrement” and a scholarship from FRSQ (VM).