Hyaluronic acid-dependent pericellular matrices in fetal fibroblasts: implication for scar-free wound repair

Abstract

Fetal fibroblasts are intrinsically different from postnatal fibroblasts. We studied the differences in expression, size, and assembly of pericellular matrices in human fetal and postnatal fibroblasts, as well as the effect of fetal fibroblast-conditioned media as a source of migration stimulating factor on pericellular matrix formation. Fibroblasts in their fifth to fifteenth passages were cultured for 24 hours before analysis. Streptomyces hyaluronidase (0.1 U/ml), monoclonal mouse anti-human CD-44std, or anti-human CD-4 antibodies were added and incubated for 1 hour (at 4 degrees and 37 degrees C) before analysis of the pericellular matrices with the use of a particle exclusion technique. The pericellular matrix/cell body ratio of fetal fibroblasts was significantly larger than that of newborn (p < 0.002) and adult (p < 0.001) fibroblasts. Hyaluronidase disrupted the pericellular matrices in all three cell lines. Assembly of the pericellular matrices was blocked by anti-human CD-44std antibody but not by anti-human CD-4 antibody at both 4 degrees and 37 degrees C. Incubation of fibroblast cell lines in fetal fibroblast-conditioned media did not increase pericellular matrix/cell body ratio but did increase the percentage of fibroblasts expressing a detectable pericellular matrix in adult (p < 0.01), newborn (p < 0.001), and fetal (p < 0.005) fibroblasts. We conclude that fibroblasts produce hyaluronic acid-dependent pericellular matrices which require interaction with a hyaluronic acid-binding protein for assembly. Large pericellular matrices are one intrinsic factor characterizing a unique fetal fibroblast phenotype.