TGF-beta and bFGF affect the differentiation of proliferating porcine fibroblasts into myofibroblasts in vitro

Fibroblasts and myofibroblasts are involved in the foreign body reaction to biomaterials, especially in capsule formation. However, contraction or det achment of the capsule can lead to complications. Biocompatibility of bioma terials may be improved by the application of proteins regulating the diffe rentiation or activation of(myo)fibroblasts. Myofibroblasts, differentiatin g from fibroblasts can be identified by the expression of alpha-smooth musc le actin (alpha-SM actin). We investigated the influence of proliferation a nd quiescence on the differentiation of porcine dermal cells and whether tr ansforming growth factor-beta (TGF-beta) and basic fibroblast growth factor (bFGF) are involved in the differentiation of proliferating cells. Porcine cells were used because pigs increasingly function as in vivo models while little is known of the characteristics of their cells. Serum-free cultured , quiescent fibroblasts differentiated into myofibroblasts, while prolifera ting fibroblasts cultured in the presence of serum containing TGF-beta, for med alpha-SM actin-negative cell clusters. After reaching confluency, these clusters started to expressing alpha-SM actin. Moreover, these proliferati ng cells produced TGF-beta from day 4 onwards while bFGF did not. Different iation into myofibroblasts was inhibited by bFGF and to an even greater ext ent by antibodies to TGF-beta. Further, two theories concerning the role of the myofibroblast in tissue contraction in view of two biomaterial applica tion will be discussed. (C) 1999 Elsevier Science Ltd. All rights reserved.