Modulating Endothelial Cell Dynamics in Fat Grafting: The Impact of DLL4 siRNA via Adipose Stem Cell Extracellular Vesicles

In the context of improving the efficacy of autologous fat grafts (AFG) in reconstructive surgery, this study delineates the novel use of adipose-derived mesenchymal stem cells (ADSCs) and their extracellular vesicles (EVs) as vehicles for delivering DLL4 siRNA. The aim was to inhibit DLL4, a gene identified through transcriptome analysis as a critical player in the vascular endothelial cells of AFG tissues, thereby negatively affecting endothelial cell functions and graft survival through the Notch signaling pathway. By engineering ADSC EVs to carry DLL4 siRNA (ADSC EVs-siDLL4), the research demonstrated a marked improvement in endothelial cell proliferation, migration, and lumen formation, as well as enhanced angiogenesis in vivo, leading to a significant increase in the survival rate of AFGs. This approach presents a significant advancement in the field of tissue engineering and regenerative medicine, offering a potential method to overcome the limitations of current fat grafting techniques.