Joris van Dongen

172 Chapter 7 In vitro studies Myofibroblasts playamajorrole inwoundhealing and scarring: activatedmyofibroblasts proliferate, produce extracellular matrix like collagens and have the ability to contract. After wound healing, myofibroblasts normally are resolved via apoptosis. However, if myofibroblasts persist, scarring will be the end result 84 . In two in vitro studies, it has been shown that trophic factors, produced by ADSC, can inhibit the myofibroblast phenotype of dermal fibroblasts after stimulation with the pro-fibrotic cytokine TGF- β 1 85 and can inhibit that of fibroblasts derived from Dupuytren’s nodules 86 . Proliferation, extracellular matrix production and contraction of these fibroblasts were reduced, which indicates that growth factors and cytokines of ADSC have the ability to prevent or even to reverse dermal scarring. FUTURE PERSPECTIVES As discussed throughout, harnessing the power of fat for fibrotic scar treatment, is an emerging concept in regenerativemedicine. Fat can however be used in several fashions: as whole adipose tissue in lipofilling, or in loose components such as SVF, ADSC or even ADSC conditioned medium. In our opinion, each of these forms has its own ideal application in regenerative medicine (Figure 3). The use of whole adipose tissue in lipofilling is optimal when there is a soft tissue defect which needs filling. Besides the ‘volumizing’ effect, scar reduction is a beneficent side effect of this treatment. Though, when extra volume is not a requirement or even a contraindication, the use of SVF offers an excellent alternative. In the setting of fibrotic dermal scars in areas where addition of extra volume is not aesthetically desirable, SVF is a good alternative for whole adipose tissue. Besides for use in dermal fibrotic scars, use of SVF opens the door for other clinical applications. Whole adipose tissue is not fit for use in fibrotic disorders in organs, such as cardiac or liver fibrosis. SVF however, would be a suitable alternative to combat organ fibrosis. SVF has all the requirements to act as a scaffold for repair, since it contains ready-to-use microvasculature, ECM and ADSC to orchestrate the repair process. For example acceleration of wound healing or alteration of early scar formation would be exemplary candidates for use of SVF. Nonetheless, in case of a pre-existing scars, a more rigorous remodeling of the mature scar tissue is necessary. Here, the microvasculature and ECM components of SVF are not a prerequisite. Thus, the application of ADSC would suffice. ADSC could orchestrate the remodeling, for example by immunomodulation or by instruction of the resident tissue cells from a synthetic to a proteolytic or a non-contractile phenotype. Last but not least, ADSC conditioned medium offers the ultimate solutionwhen only instructive (growth) factors