Reply: Systemic Administration of Adipose-Derived Stromal Cells Concurrent with Fat Grafting

Sir: We would like to thank Dr. Choudhery for his interest and thoughtful comments on our article.1 In this study, we elucidated adipose-derived stromal cell homing after intravenous injection concurrent with fat grafting. We highlighted the therapeutic value of cell-assisted lipotransfer by demonstrating improved graft retention via a new delivery method rather than by mixing adipose-derived stromal cells with fat. The first issue is a homing of intravenously injected adipose-derived stromal cells to the graft and its underlying mechanism. We observed DsRed adipose-derived stromal cells in the graft at postoperative weeks 1, 4, and 8 without cell counting. Considering the proliferative capacity of stem cells, it would be better to measure the number of DsRed adipose-derived stromal cells in the graft a few days after injection to determine the exact proportion of homing. As we discussed in the limitations of our study, we lacked an explanation of the cellular and molecular mechanisms of homing. Thus, further mechanistic research is needed to deliver the intended amount of cells to a precise location. The second issue is the number and passage of adipose-derived stromal cells. We injected 1.0 × 105 DsRed adipose-derived stromal cells from passages 3 through 7. The number of cells was small compared to our previous study, in which 2.5 × 105 or 1.0 × 106 DsRed adipose-derived stromal cells were delivered by mixing with grafted fat.2 However, we expected that a large number of intravenously injected cells would cause animal death due to embolism.3 Thus, further research on the optimal number of injected cells is needed to ensure safety. In terms of cell passage, we were able to obtain consistent experimental results in the previous and present study.1,2 Nonetheless, we are aware of the limitations of the primary culture, and we will try to use early passage cells in the next experiment.4 The third issue is the cell delivery method. Using a retrobulbar approach through the retro-orbital sinus, we intravenously delivered DsRed adipose-derived stromal cells.5 The retrobulbar approach, instead of the tail vein approach, was chosen to increase the success rate of cell delivery from a technical perspective. However, as he mentioned, it would be interesting to analyze adipose-derived stromal cell tracing among different delivery methods, including direct, intravenous (retrobulbar and tail vein approaches), and intraperitoneal approaches. We agree that supplementation with stromal vascular fraction cells or adipose-derived stromal cells in fat grafts can be an attractive alternative to overcome critical limitations such as low graft retention. However, further research related to cell-assisted lipotransfer is needed to define optimal conditions, such as cell number, injection number, and delivery method; to understand the underlying mechanism; and to ensure clinical long-term safety. Once again, we thank him for his interest in our article and for raising important issues that need to be discussed. DISCLOSURE None of the authors has a financial interest to declare in relation to the content of this communication. Ki Yong Hong, M.D., Ph.D.Department of Plastic and Reconstructive SurgeryDongguk University Medical CenterGoyang, Korea Il-Kug Kim, M.D., Ph.D.Department of Plastic and Reconstructive SurgeryYeungnam University College of MedicineDaegu, Korea Seong Oh Park, M.D.Department of Plastic and Reconstructive SurgeryCollege of Medicine, Hanyang UniversitySeoul, Korea Ung Sik Jin, M.D., Ph.D.Hak Chang, M.D., Ph.D.Department of Plastic and Reconstructive SurgerySeoul National University College of MedicineSeoul, Korea