Joris van Dongen

168 Chapter 7 ECM influences morphogenesis and migration speed depends on ECM density during angiogenesis 70 . Furthermore, ECM functions as a scaffold for other cell types at the site of injection. The interaction of cellular integrins, i.e. matrix receptors, suppresses pro- apoptotic signaling. Thus, applications that include intact, non-enzymatic, generated SVF might favor graft survival. However, only mechanical isolation of SVF preserves ECM, while enzymatic isolation of SVF disrupts all communicative connections between cells. As compared to cultured ADSC and in vitro studied growth factors, freshly isolated SVF contain cells with still their in vivo phenotype and growth factor secretion respectively. As compared to lipofilling, the use SVF might avoid possible complications like cyst formation or overfilling 71 : because only small volumes (less than ten milliliters) of SVF are injected. Thus, since injected volume is limited, there is no risk of overfilling. Since no adipocytes are injected, there is also no risk of oily cyst formation. ADSC AS AN ANTI-SCARRING TREATMENT Clinical studies To date, the use of ADSC as a cell therapy for treatment for fibrosis has not been thoroughly investigated in clinical studies. ADSC have been applied in two non- controlled, non-randomized studies investigating the effect of ADSC-enriched lipografts on healing of chronic, intractable radiation ulcera in 10 patients 72 and for correction of soft tissue defects in 29 patients 73 . It was concluded that ADSC improve wound healing 72 and fat graft take 73 and concomitantly decrease deep tissue fibrosis and dermal scarring. However, fundamentally, there is ample evidence for these effects: ADSC increase angiogenesis, can induce mitosis in resident tissue cells and are able to remodel ECM. Based on the design of both studies, no definitive conclusions can be drawn on the effectiveness of the use of ADSC as scar treatment. On the other hand, studies in the field of cell-assisted lipotransfer (CAL), where lipografts are combined with ADSC in order to improve fat graft survival, there have been several properly designed, controlled clinical trials 74-76 to demonstrate the efficacy of CAL for improvement of lipograft survival over lipofilling alone. In these studies no serious adverse eventswere reported after injection of autologous freshly isolated 74,75 or culture expanded 76 ADSC. It can be concluded that use of autologous ADSC in patients is safe. These clinical trials warrant the dissection of the underlying mechanism via animal models and in vitro investigations of underlying molecular pathways.