Reply: Extracellular Vesicles from Human Adipose-Derived Stem Cells for the Improvement of Angiogenesis and Fat-Grafting Application.

Abstract

Sir: We thank Drs. Qu and Luan for their interest in our recent report,1 which indicates the potential application of adipose-derived mesenchymal stem cell–derived extracellular vesicles in fat transplantation. Because the robust angiogenesis of human adipose-derived stem cells has been proved in many studies, it is easy to infer that the adipose-derived mesenchymal stem cell–derived extracellular vesicles, which possess similar contents of adipose-derived stem cells (i.e., miRNAs, proteins), could also improve the birth of neovessels. In addition, scientists have demonstrated the stem cell extracellular vesicles’ priority on long-term storage and immunogenicity compared with stem cells. Therefore, it is our main target to supply convincing evidence about potential use of adipose-derived mesenchymal stem cell–derived extracellular vesicles in fat transplantation for plastic surgery operations. For this reason, we optimized our in vivo experimental design by comparing the in vitro effect of different concentrations of adipose-derived mesenchymal stem cell–derived extracellular vesicles. In addition, we believe the in vitro results of the 20-μg/ml group would be suitable to be representative because of the balance of economy and effectiveness. We agree that various dosages of extracellular vesicles can be used in vivo to confirm an effective physiologic range for adipose-derived mesenchymal stem cell–derived extracellular vesicles for further use. With regard to the body mass index of donors in our study, it is really an important data point for the reader, and we chose donors whose body mass index ranged from 23 to 29 kg/m2. Several previous studies have showed that it is a rather complex process in the early stage of fat transplantation.2 Remodeling of fat tissue and the birth of neovessels occur at different time points. In our vitro results, adipose-derived mesenchymal stem cell–derived extracellular vesicles could be taken in by cells in less than 4 hours. Therefore, it could be inferred that when mixed with grafts, adipose-derived mesenchymal stem cell–derived extracellular vesicles could only affect the activity of macrophages or endothelial cells in vivo for a very short time. More potential mechanisms are now studied by our team, and we thank Drs. Qu and Luan for their interest in our recent report again. DISCLOSURE The authors have no financial interest to declare in relation to the content of this communication.