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 detachment of the capsule can lead to complications. Biocompatibility of biomaterials may be improved by the application of proteins regulating the differentiation or activation of (myo)fibroblasts. Myofibroblasts, differentiating from fibroblasts can be identified by the expression of alpha-smooth muscle actin (alpha-SM actin). We investigated the influence of proliferation and quiescence on the differentiation of porcine dermal cells and whether transforming 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 proliferating fibroblasts cultured in the presence of serum containing TGF-beta, formed alpha-SM actin-negative cell clusters. After reaching confluency, these clusters started to expressing alpha-SM actin. Moreover, these proliferating cells produced TGF-beta from day 4 onwards while bFGF did not. Differentiation into myofibroblasts was inhibited by bFGF and to an even greater extent by antibodies to TGF-beta. Further, two theories concerning the role of the myofibroblast in tissue contraction in view of two biomaterial application will be discussed.