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Abstract
Scar tissue formations arise subsequent to dermal injury, and are the end point of normal mammalian tissue repair. The ideal end point of wound healing is total repair, with functional characteristics and without scar formation; however, inflammation and incomplete collagen remodelling are known to hinder adult wound healing. In adult humans, injured tissue are repaired by collagen deposition, collagen remodelling and eventual scar formation, where fetal wound healing is believed to be more of a regenerative process that is rapid, has little inflammation and can restore skin function without scar formation.
The primary focus of research currently is on the skin’s composition and the unique environment that the foetus is found in, none of which report the differences in protein and secretome composition between foetal and adult fibroblasts. It is widely agreed that having the ability to modulate certain key proteins in the adult wound may minimise the scarring of a wound. Therefore, it is hypothesised that the addition of combinations of wound healing promoting compounds: α-lipoic acid, N-acetylcysteine, resveratrol, γ-glutamylcysteine, ectoine and emlica will be able to modulate the proteomic profile of human adult fibroblasts (HAF) to more closely match the profile determined in human foetal fibroblasts (HFF) and could potentially lead to a reduction in scar tissue formation in adult skin.
This study utilised an expression proteomics approach to profile the proteome and secretome from Human adult and foetal dermal fibroblasts, HAF and HFF respectively. Two-dimensional electrophoresis and 3D gel densitometry were used to generate protein fingerprints and comparative protein expression levels between the two cell lineages. HAF were then cultivated in the presence of various concentrations of individual compounds and a battery of cytotoxicity tests was performed. Beneficial concentrations of the compounds were combined into 72 different combinations in a factorial experiment and cytotoxicity tests subsequently conducted. Combinations were culled according to their performances with each test. HAF were grown in the presence of the final two optimum concentrations and the proteome and secretome of the cells were compared to HFF to investigate if the profile has been modulated to mimic a HFF profile.
This study identified that the proteome and secretome of HFF and HAF have different protein expression patterns, with a potential discovery of novel pathways. Proteins that may have a role to play in scarring were also identified. It was determined that growing HAF in the presence of the right combination of compounds can modulate the proteomic profile of the cells, and a combination that modified the profile of HAF to more closely match that of untreated HFF was developed.
In conclusion, this study may facilitate an insight into the complex proteome system of dermal fibroblasts and identify tentative biomarkers during scarless wound healing. Collectively, this study suggests that the profile of proteins identified in HAF grown in the presence of the final combinations can be modulated, resulting in the possibility to design therapeutic strategies that may prevent scarring following wounds to the dermis.