Fetal Dermal Fibroblasts Retain a Hyperactive Migratory and Contractile Phenotype Under 2-and 3-Dimensional Constraints Compared to Normal Adult Fibroblasts

Abstract

Fetal dermal fibroblasts participate in a dramatically different wound healing process compared to their adult counterparts, and it is thought that their intrinsic phenotype contributes to the unique properties of fetal repair. In particular, fibroblast migratory and contractile properties have been shown to be important in the development or lack of fibrosis/scarring. Despite extensive study to date, and multiple experimental techniques utilized by various laboratories, the precise differences between fetal and adult dermal fibroblasts remain unclear. We characterized the migratory and contractile dynamics of fetal dermal fibroblasts at the individual cell and population levels under both 2-dimensional (2D) and 3-dimensional (3D) constraints. Data indicate that (1) individual fetal fibroblasts attach and locomote quicker than adult fibroblasts, resulting in faster migration at the population level; (2) use of a 2D bioactive matrix (collagen) dramatically speeds up the transition from attachment to locomotion; and (3) fetal fibroblasts compact 2D collagen matrices faster than adult fibroblasts. These characteristics are maintained inside of a novel 3D construct, which approximates some in vivo tissue repair dynamics. Specifically, fetal fibroblasts invade this construct faster than adult fibroblasts, likely through more dynamic interactions with surrounding collagen fibers. In conclusion, the hyperactive migratory and contractile dynamics of fetal fibroblasts are qualitatively and quantitatively conserved despite transitions from individual cells to whole populations and from 2D to 3D constraints. We conclude that fetal fibroblasts display a robust phenotype, which is only partially altered by changes in substrate and geometric constraints. This phenotype likely is important in dictating the dynamics of fetal tissue repair.