Joris van Dongen

169 The power of fat and ASCs for scar treatment: a review Animal studies In animal wound healing models, where ADSC were used to speed up wound healing 77- 80 it was observed that ADSC reduce severity of scarring after wound closure (Table 3). ADSC improved the wound healing rate in three out of four studies and smaller fibrotic areas remained after wound healing 77 . Yet, the epidermal thickness increased 79,80 , and the gene expression of the pro-fibrotic markers α -smooth muscle actin and TGF- β 1 decreased 79,80 while the gene expression of anti-fibrotic fibroblast growth factor and pro-angiogenic VEGF 79 increased. Together, this indicates that in vivo administered ADSC, suppress the formation of dermal scar, through augmented wound healing. The comparison with clinical treatment of pre-existing scars is hampered, because these animal studies more prevent scar formation than revert pre-existing scars. In animal models specifically designed to study scarring 81,82 and to study the fibrotic disorder of Peyronie’s disease 83 (Table 3), it was noted that deposition of extracellular matrix components, such as collagen type I and III and elastin, was decreased after treatment of scars with ADSC. Also, collagen fiber alignment improved in the treated scar areas 81,82 . Functionally, treatment of scars with ADSC lead to smaller scars 81 and less scar elevation 81 . Together, we surmise that the remodeling of the fibrotic matrix in a scar by ADSC is one of the components that governs scar reduction. Interestingly, ADSC are derived from connective tissue (SVF of fat), but appear to act as ‘good guys’ in contrast to the scar myofibroblasts, which are connective tissue cells too, but ‘bad guys’. The ADSC are capable of tilting the balance between ECM deposition and ECM degradation in favor of degradation.Whether this depends solely onmatrix influence or also on direct influence on the scar-resident myofibroblast remains to be investigated. In conclusion, treatment of wounds or mature scars with ADSC in different animal models have shown to result in faster wound healing and reduction of scar tissue on both macroscopic and microscopic level. Thus, use of autologous ADSC to improve wound healing and to prevent or diminish scar tissue in patients, seems to be a very exciting and promising way to go.

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