Early activation of macrophage-2 with IL-4 in stromal vascular fraction increases VEGF levels and adipocyte count and maintains volume of fat graft in Wistar rats (Rattus norvegicus)

Several previous studies have demonstrated the benefits of early macrophage 2 activation fat grafts supplemented with macrophage culture. However, this approach is considered impractical in clinical settings because of intraperitoneal induction use. The aim of this study was to investigate the effect of early stromal vascular fraction (SVF) macrophage-2 activation with IL-4 on fat graft survival compared to SVF alone using an animal model for better fat graft viability. This experimental study included inguinal fat harvesting, isolated with collagenases to retrieve the SVF, and then injected with a combination of fat graft and SVF (0.3 mL) into the scalp region. The intervention group received an IL-4 intralesional injection on the third day, and the fat grafts were biopsied on days 7, 14, and The primary outcomes were the final volume of the fat graft, vascular endothelial growth factor (VEGF) expression, and the adipocyte cell count using perilipin staining on immunohistochemistry examination. The group receiving IL-4 exhibited significantly higher VEGF on days 7, 14, and 30 (<i>p</i> = 0.009, 0.009, and 0.021, respectively). Similarly, the IL-4 treatment significantly increased the perilipin concentration on days 7, 14, and 30 (<i>p</i> = 0.008, 0.008, and 0.029, respectively). In this group, VEGF concentration was significantly increased on day 14 as compared to day 7 (<i>p</i> = 0.009), while no significant difference was observed in the control group (<i>p</i> = 0.090). Additionally, the IL-4 group displayed significantly less reduction of fat graft volume than the control group, as observed on days 7, 14, and 30 (<i>p</i> = 0.009, 0.009, and 0.021, respectively). Overall, the study underscores the potential benefits of early M2 polarization in fat grafting, as well as providing practical advantages for improving fat graft volume retention.