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

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Sir: We read with great interest the article by Mou et al. entitled “Extracellular Vesicles from Human Adipose-Derived Stem Cells for the Improvement of Angiogenesis and Fat-Grafting Application.”1,2 In this study, the authors evaluated whether adipose-derived mesenchymal stem cell–derived extracellular vesicles improved fat graft survival by angiogenesis and inflammation regulation. We admire the achievements the authors demonstrated, namely, that adipose-derived mesenchymal stem cell–derived extracellular vesicles promoted the migration and tube formation of human umbilical vein endothelial cells. In addition, this study showed the vesicles attenuated the inflammation response through polarizing M2 macrophages. However, we would like to advance a few questions and perspectives. First, the authors presented that adipose granules co-transplanted with 7 μg of extracellular vesicles had a better survival retention of fat grafts. Only one dose was chosen in the experimental group. However, the results may not be enough to prove the regenerative potential of the vesicles without comparing different dosages. We would appreciate it if the authors would provide the details on the basis of concentration used in this study. Thus, we suggest that researchers should incorporate various dosages of extracellular vesicles to confirm an effective physiologic range. Second, the lipoaspirates were obtained from five women, aged 20 to 40 years. However, the authors did not provide the range of body mass index of donors. As far as we know, obesity could extend to metabolic and endocrine dysfunction; these adipose-derived stem cells express higher mRNA levels of several proinflammatory cytokines compared with healthy adipose-derived stem cells.3 Therefore, the production and bioactivity of the exosomes for obesity adipose-derived stem cells would be negatively influenced. The recent advances in our understanding of adipose-derived stem cells have made it essential to identify the donor source of cells to ensure consistent therapeutic efficacy. Third, fat grafts were harvested and analyzed from four randomly selected mice of each group in this study. Nevertheless, Eto et al. revealed that adipocytes were most susceptible to death after fat grafting under ischemic conditions, whereas adipose-derived stromal cells can remain viable for 3 days and had regenerative activities.4 In addition, according to the research by Kato et al., CD34+ proliferating adipose stem/progenitor cells were seen at 1 to 4 weeks, but the majority of proliferating cells were M2 macrophages.5 Therefore, the timing of observation might not be accurate enough for us to see the dynamic remodeling impacted by extracellular vesicles after fat grafting. In conclusion, we are very grateful that the authors demonstrated that adipose-derived mesenchymal stem cell–derived extracellular vesicles had proangiogenic and antiinflammatory effects on nonvascularized fat grafting. This work laid a great foundation for further research and clinical application in this field. We expect further findings that the adipose-derived mesenchymal stem cell–derived extracellular vesicles may possess regenerative potential for innovative medical products in clinical translation. DISCLOSURE The authors have no financial interest to declare in relation to the content of this communication.