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The altered mechanical phenotype of fetal fibroblasts hinders myofibroblast differentiation.

Jerrell RJ, Leih MJ, Parekh A
Wound Repair Regen. 2019 27 (1): 29-38

PMID: 30315715 · PMCID: PMC6378408 · DOI:10.1111/wrr.12677

During the dermal wound healing process, the mechanical rigidity of the newly deposited extracellular matrix and transforming growth factor-β1 promote the transition of fibroblasts into myofibroblasts. Myofibroblasts generate large cellular forces that contract and remodel the extracellular matrix leading to scar formation. In contrast, myofibroblasts are not detected in fetal dermal wounds which are more compliant and contain less transforming growth factor-β1 than adult wounds. Instead, fetal fibroblasts orchestrate scarless healing of dermal wounds resulting in healed tissues that resemble uninjured dermis. While these biomechanical differences suggest that the fetal wound environment promotes smaller cellular forces which enable regeneration, previous studies indicate that fetal fibroblasts have unique contractile properties that may facilitate scarless dermal repair. Therefore, we tested whether physiologic wound rigidities and transforming growth factor-β1 induce contractile forces and myofibroblast differentiation of fetal dermal fibroblasts. In comparison to their adult dermal counterparts, we found that fetal fibroblasts exhibit a deficient contractile response to rigid extracellular matrix and transforming growth factor-β1. Our data suggest that the contractile phenotype of fetal dermal fibroblasts limits their cellular force production and prevents their ability to differentiate into myofibroblasts.

© 2018 The Authors. Wound Repair and Regeneration published by Wiley Periodicals, Inc. on behalf of by the Wound Healing Society.

MeSH Terms (18)

Adult Cell Differentiation Cells, Cultured Cicatrix Collagen Type III Extracellular Matrix Female Fetus Fibroblasts Gene Expression Regulation Humans Male Myofibroblasts Phenotype Pregnancy Transforming Growth Factor beta1 Wound Healing Young Adult

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