Grants We Funded

Abstract
The central hypothesis of our project is that fetal and adult keratinocytes (FKs, AKs) interact with fetal and adult fibroblasts (FFs, AFs) through TGF-B in promoting scarless repair. Scarless fetal wound healing is a paradigm for ideal tissue repair. However, the biology responsible for this phenomenon is poorly understood Understanding scarless healing has profound implications in plastic surgery, in diverse areas such as bum, cleft lip and breast implant surgery. Surgical treatment is limited by scarring and need for additional surgery. Developing methods to promote scarless healing will play a critical role in improving treatment modalities. Until recently, the mechanisms and interactions regulating scarless wound healing have remained largely unknown. Our previous work suggests that the fetal fibroblast, which produces collagen and the extracellular matrix, is the cell type primarily responsible for scarless skin repair. In addition, we have shown that keratinocytes, in co-culture with fibroblasts, influence fibroblast cell biology. However, the function of the fetal keratinocyte during the fetal repair process has not been investigated and remains unknown. Based on our preliminary data, we have focused on TGF-B as a prototype growth factor which has function both during scarless and scarring repair that is determined by differential expression of ligand, receptors, and modulators. Our research will examine TGF-B biology in a co-culture model containing FKs, AKs, FFs and AFs in mix and match combinations. We hypothesize that FK-derived and AK derived TGF-B is responsible for the changes in FF and AF cell biology found when co-cultured Furthermore, we anticipate that fetal keratinocytes can influence adult fibroblasts to behave more fetal-like through TGF- B expression resulting in increased ratio of Type III to Type I Collagen and an altered extracellular matrix profile. There are three specific aims for this project. They are: 1) To determine TGF-B expression in fetal and adult keratinocytes (FKs, AKs) cultured in isolation; 2) To determine TGF-B expression in FKs and AKs co-cu1tured with fetal and adult fibroblasts (FFs, AFs); and 3) To determine the extent of TGF-B activation in these culture sets and its influence on fetal and adult fibroblasts with regards to collagen expression and the extracellular matrix profile. By examining the interaction of fetal fibroblasts and fetal keratinocytes compared to their adult counterparts, we troy begin to understand ways to promote Scarless healing. The implications of understanding fetal repair have tremendous appeal for physicians and scientists, because this knowledge may one day allow us to manipulate adult wound healing to decrease scarring and fibrosis in plastic surgery as well as in surgery of other organs of the body.