Fat, fibroblasts, and fibrosis: how deposits of adipose tissue ameliorate dermal scarring

Hypertrophic dermal scarring is a debilitating condition for which there is no effective treatment. Autologous fat grafting is a rapidly developing technique able to regenerate scar tissue. Hypertrophic scarring is a result of dysregulated extracellular matrix deposition from an increased myofibroblast presence. Following fat grafting, scar tissue contains a lower population of myofibroblasts and a remodelled extracellular matrix. Adipose tissue used in fat grafting is often processed to form different clinical formulations before grafting. It has been suggested that a population of stromal cells contained within adipose tissue can inhibit fibroblast to myofibroblast differentiation. However, there has been no in vitro demonstration that clinically relevant formulations of adipose tissue can inhibit myofibroblast differentiation. Here it is shown that paracrine factors, secreted from forms of adipose tissue used in a clinical setting, can inhibit, and reverse the differentiation of myofibroblasts in vitro. The clinical formulations of adipose tissue chosen for this work were; lipoaspirate, Nanofat-like adipose tissue, stromal vascular fraction-gel, and adipose derived stem/stromal cells. Cell culture medium conditioned with paracrine factors from these formulations was able to prevent expression of myofibroblast markers in TGF-β1 treated fibroblasts. Additionally, when applied to differentiated myofibroblasts, adipose tissue-derived conditioned medium lowered the expression of α-SMA. These results are the first to demonstrate that factors released from different formulations of adipose tissue can inhibit and reverse myofibroblast differentiation in an in vitro model simulating the onset of scarring. This knowledge gives an insight into the clinical use of autologous fat grafting and suggests a mechanism for how fat grating treatments can remodel the extracellular matrix found in scar tissue. The data presents clear evidence that fat grafting can lower the myofibroblast population in hypertrophic scars and prevent new myofibroblasts from differentiating. This allows for a decrease in extracellular matrix tension and a lowering of scar morbidity.