Fetal and postnatal sera differentially modulate human dermal fibroblast phenotypic and functional features in vitro
✍ Scribed by Véronique Moulin; François A. Auger; Maureen O'Connor-McCourt; Lucie Germain
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 483 KB
- Volume
- 171
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Fetal wounds heal without scar formation, fibrosis, or contracture. Compared with adult wounds, they are characterized by major differences in the extracellular matrix and the absence of myofibroblastic cells. The reasons for these differences are not well known and determination of factors affecting the absence of scarring in the fetus may lead to strategies for controlling adult pathological scarring. In the present study, we have assessed the effects of serum on the behavior of normal human dermal fibroblasts. Using an in vitro approach, we investigated the effects of fetal and adult serum on cell properties such as growth rate, collagen synthesis, gelatinase activities, and differentiation to myofibroblasts using biochemical, morphological, and ultrastructural parameters. We studied the induction of a-smooth muscle (a-SM) actin in fibroblasts, and its correlation with increased collagen gel contraction by the cells. Our results showed that, compared with FBS (fetal bovine serum), postnatal calf serum (PCS) decreased mitogenic activity and collagenase synthesis but not collagen synthesis. Furthermore, cells cultured with PCS differentiated to myofibroblasts with an increase in cell diameter, number of stress fibers, a-SM actin expression, and collagen gel contraction. To characterize the molecules involved in this differentiation process, the amount of transforming growth factor b (TGFb) in FBS and PCS was determined and the effect of neutralizing anti-TGFb antibody was evaluated. It was determined that FBS contained more TGFb than PCS, but that essentially all the TGFb was latent in both sera. However, results obtained with anti-TGFb antibody show that active TGFb is present when human dermal fibroblasts are cultured with medium containing PCS. These results suggest that, in the presence of PCS but not FBS, the cells either produce active TGFb or an enzyme that is able to activate latent serum TGFb. Alternatively, sera may contain two different forms of latent TGFb, the PCS form being activated by the dermal fibroblast cells. A similar mechanism may be involved, at least in part, in skin wound healing and may underlie the appearance of myofibroblasts in postnatal wounds.