Abstract: Fat grafting is a simple and minimally invasive approach for soft tissue reconstruction; however, poor graft engraftment due to insufficient vascularization remains a major challenge. Previous studies have shown that the addition of adipose-derived stem cells (ADSCs) to fat grafts enhances angiogenesis and improves engraftment. However, extracting autologous ADSCs requires invasive procedures and specialized facilities, limiting their widespread adoption in clinical practice. Despite ADSCs having both angiogenic and immune-tolerant properties, most studies have focused on autologous transplantation in immunodeficient models, and the efficacy and mechanisms of non-autologous transplantation under immune response remain unclear. To address this issue and aim for the realization of off-the-shelf fat grafting using pre-formulated, non-autologous ADSCs for immediate transplantation, we aimed to evaluate the potential of non-autologous ADSCs by using human ADSCs and immunocompetent mice. To better mimic the in vivo environment, human ADSCs were 3D-cultured, resulting in significant upregulation of angiogenic markers compared to 2D cultures. Fat grafts containing only human adipocytes (adipocyte-only group) and fat grafts supplemented with ADSCs (ADSC-supplemented group) were transplanted subcutaneously into immunocompetent mice and analyzed using immunohistochemical staining for fat engraftment and vascularization. In the adipocyte-only group, human fat was completely resorbed within 4 weeks, with no evidence of angiogenesis. In contrast, the ADSC-supplemented group demonstrated sustained graft engraftment even at 3 months, along with significant neovascularization. Furthermore, both the ADSCs and the transplanted adipocytes were non-autologous in this experiment. These findings suggest that non-autologous ADSCs not only promote angiogenesis under immune response conditions but also facilitate the engraftment of non-autologous fat grafts otherwise expected to face immune rejection, indicating the potential to achieve fat grafting solely with non-autologous cells. Our findings pave the way for an off-the-shelf, novel approach to regenerative medicine in soft tissue reconstruction.
Funding Source: This study was funded by Rohto Pharmaceutical Co., Ltd.
