Joris van Dongen

12 Chapter 1 promote risk for breast cancer in mastectomized patients. Coleman understood that consistent results of lipofilling could be achieved by developing better techniques and instruments for harvesting, processing and injecting lipoaspirate. 16-18 He developed very fine cannulas to harvest and inject smaller particles of adipose tissue and showed it was possible to transplant adipose tissue in areas were only small amount of fat are needed, such as in the hands or in the face. Injection of smaller sized graft fragments using smaller holes in harvesting cannulas as well as for injection could increase volume retention. 19 Smaller sized fat grafts most likely engraft better due to faster connection to donor vasculature and no diffusion barrier resulting in more living cells in the core. Yet, the results remained rather unpredictable and the fate of the injected adipocytes was still unknown. The fate of injected adipocytes To date, two main theories about the fate of injected adipocytes have been described in literature. The first theory is the ‘host cell replacement theory’ described by Neuhof and Hirshfeld in 1923. 20 The ‘host cell replacement theory’ stated that transplanted adipose tissue completely necrotized in a few months after transplantation and is replaced by fibrotic tissue or newly formed metaplastic adipocytes. The transplanted adipose tissue functions as a scaffold for ingrowth of newly formed fibrotic or adipose tissue both from recipient origin. 20 The second theory is the ‘cell survival theory’ introduced by Peer in 1955. 21 The ‘cell survival theory’ assumed that (part of ) the fat graft survived after transplantation. Survival of transplanted cells in fat grafts depends on capillary ingrowth of recipient vessels and formation of anastomosis between donor and recipient vessels. 21 Formation of anastomosis or angiogenesis is induced by the occurrence of hypoxia due to the delay between harvesting and injecting lipoaspirate. 22,23 However, mature adipocytes are sensitive to hypoxia and trauma induced by harvesting, processing and injection of fat grafts resulting in apoptosis. 24-26 Adipocytes that are located more favourably i.e. close to newly formed anastomosis in the periphery and therefore shorter exposed to hypoxia tend to survive longer. 21 On the other hand, adipocytes secrete more vascular endothelial growth factor under hypoxia stimulating angiogenesis. 27 The survival of more cells in the periphery of transplanted adipose tissue was later confirmed by Carpaneda and Ribeiro showing that five days postoperative after transplantation three zones i.e. peripheral zone, intermediate zone and central zone surrounded by a collagen capsule could be distinguished. 28