A Comparison of the Ability of Intra-oral and Extra-oral Fibroblasts to Stimulate Extracellular Matrix Reorganization in a Model of Wound Contraction

Abstract

Intra-oral wounds, like wounds in children, demonstrate privileged healing when compared with adult wounds at extra-oral sites. This study investigated whether this preferential healing is related to an increased ability of oral mucosal fibroblasts to reorganize extracellular matrix (ECM) when compared with their dermal counterparts. ECM reorganization was investigated by means of a fibroblast-populated collagen lattice (FPCL) system. The effect of donor age was also investigated in this system. Differences in ECM reorganization and FPCL contraction were evident: FPCL contraction was more rapid by oral mucosal fibroblasts than dermal fibroblasts (p < 0.01). FPCL contraction was also greater in child (donor < 10 years) than adult (donor > 18 years) oral mucosal fibroblasts (p < 0.01). These differences were not related to phenotypic differences in cell viability (p > 0.5), DNA synthesis (p > 0.05), and cell number (p > 0.5) within the FPCLs, or cellular attachment to collagen (p > 0.07). FPCL contraction was not stimulated by the addition of conditioned medium from oral mucosal or dermal fibroblasts (p > 0.05). These data show that the significantly increased ability of oral mucosal fibroblasts to reorganize ECM in vitro, when compared with dermal fibroblasts, represents a distinct phenotypic contractile difference, rather than differences in their production of soluble mediators or cell attachment to ECM.

Crosslinking and G-protein functions of transglutaminase 2 contribute differentially to fibroblast wound healing responses

“…Cultures of primary foreskin fibroblasts were established as described previously (Stephens et al, 1996) and maintained in DME medium supplemented with 2 mM L-glutamine, non-essential amino acids, antibiotics (100 U/ml penicillin, 100 µg/ml streptomycin, 0.25 µg/ml amphotericin B) and 10% FCS at 37°C in a 5% CO2 humidified atmosphere. Prior to seven population doubling levels (PDLs) cells were considered primary cells.…”

Involvement of Hyaluronan in Regulation of Fibroblast Phenotype

“…However, wound healing in the oral mucosa is clinically distinguished from dermal healing in terms of both its rapidity and lack of notable scar formation. Previous in vitro work has demonstrated that oral mucosal fibroblasts show increased migration, experimental wound re-population, and ECM re-organization compared with dermal fibroblasts (35,36). Consequently in trying to understand fibrosis, we have used dermal and oral mucosal fibroblasts as models of scarring and nonscarring fibroblast phenotypes, to identify the processes that underlie scar-free healing.…”

Small Cytoskeleton-Associated Molecule, Fibroblast Growth Factor Receptor 1 Oncogene Partner 2/Wound Inducible Transcript-3.0 (FGFR1OP2/wit3.0), Facilitates Fibroblast-Driven Wound Closure

“…The inflammatory response in wounded oral mucosa is less intensive than in skin, 6 and the expression of cytokines is also low in oral wounds during the healing period. [7][8][9][10][11] Saliva contains a group of cytokines, 12,13 which may provide a unique oral environment suitable for wound healing. However, skin grafts transposed into the oral cavity maintain the skin wound healing phenotype, 14 indicating that constitutive oral cellular phenotypes, not the oral environment, may play the primary role in the oral wound healing.…”