Improving Autologous Fat Grafting in Regenerative Surgery through Stem Cell-Assisted Lipotransfer.

Autologous fat transplantation -i.e., lipofilling- has become a promising and popular technique in aesthetic and reconstructive surgery with several application such as breast reconstruction, facial and hand rejuvenation. However, the use of this technology is still limited due to an unpredictable and low graft survival rate (which ranges from 25%-80%). A systematic literature review was performed by thoroughly searching 12 terms using the PubMed database. The objective of this study is to present the current evidence for the efficacy of adjuvant regenerative strategies and cellular factors, which have been tested to improve fat graft retention. We present the main results (fat retention rate, histological analysis for pre-clinical studies and satisfaction/ complication for clinical studies) obtained from the studies of the three main fat grafting enrichment techniques: platelet-rich plasma (PRP), the stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) and discuss the promising role of recent angiogenic cell enrichment that could induce early vascularization of fat graft. All in all, adding stem or progenitor cells to autologous fat transplantation might become a new concept in lipofilling. New preclinical models should be used to find mechanisms able to increase fat retention, assure safety and transfer these technologies to a good manufacturing practice (GMP) compliant facility, to manufacture an advanced therapy medicinal product (ATMP).

Human ESC-derived MSCs enhance fat engraftment by promoting adipocyte reaggregation, secreting CCL2 and mobilizing macrophages.

Mesenchymal stem cells (MSCs) derived from somatic tissues have been used to promote lipotransfer, a common practice in cosmetic surgery. However, the effect of lipotransfer varies, and the mechanism of action remains vague. To address these questions, we differentiated human embryonic stem cells, a stable and unlimited source, into MSCs (EMSCs). Then we subcutaneously transplanted human fat aspirates together with EMSCs or PBS as a control into the back of nude mice. Within 24 h of transplantation, EMSCs promoted aggregation and encapsulation of injected fat tissues. Afterward, all grafts gradually shrank. However, EMSC-containing grafts were larger, heavier and had fewer dark areas on the surface than the control grafts. Histologically, more live adipocytes, vascular cells, and macrophages and less fibrosis were observed in EMSC-containing grafts than in the controls. Some EMSCs differentiated into vascular cells and adipocytes in the EMSC-containing grafts. RNA sequencing revealed that human RNA was shown to decline rapidly, while mouse RNA increased in the grafts; further, human genes related to extracellular matrix remodeling, adipogenesis, and chemokine (including CCL2) signaling were expressed at higher levels in the EMSC-containing grafts than they were in the controls. CCL2 knockout reduced macrophage migration towards EMSCs in vitro and early macrophage recruitment to the grafts and the pro-engraftment effect of EMSCs in vivo. Treating mice with a macrophage inhibitor abolished the EMSC effects and converted the grafts to heavy masses of cell debris. Together, these data demonstrate that EMSCs promote fat engraftment via enhanced tissue reconstitution and encapsulation of implanted tissues, which was followed by increased angiogenesis and adipocyte survival and reduced fibrosis, in which stimulated CCL2 signaling and mobilized macrophages play pivotal roles.