Quality and Quantity–Cultured Human Mononuclear Cells Improve Human Fat Graft Vascularization and Survival in an In Vivo Murine Experimental Model

We read with tremendous interest the article entitled “Quality and Quantity–Cultured Human Mononuclear Cells Improve Human Fat Graft Vascularization and Survival in an In Vivo Murine Experimental Model.”1 The article is thought-provoking, and we would like to add some additional perspectives that might extend the current results. First, an interesting finding is that stromal vascular fraction did not increase vessel density but enhanced the weight persistence of fat by week 7; therefore, the authors thought stromal vascular fraction might function not through angiogenesis. However, some studies have demonstrated that stromal vascular fraction could enhance vessel growth. Matsumoto et al.2 implanted free fat supplemented with stromal vascular fraction in mice and found that stromal vascular fraction–assisted fat exhibited more microvasculature than the non–stromal vascular fraction fat. In a mouse model of wound healing,3 stromal vascular fraction significantly increased the density of CD31-positive vessels compared with the control mice. One explanation might be that the authors extracted stromal vascular fraction from middle-aged individuals rather than younger ones, which would possibly limit the capacity of stromal vascular fraction to support microvascular networks. Allison L. Aird’s team4 implanted collagen constructs into mice that contained either young stromal vascular fraction (from a 4-month-old rat) or old stromal vascular fraction (from a 24-month-old rat). Their findings demonstrated that mean total vessels, perfused vessels, and mature vessels were reduced in the old stromal vascular fraction group compared with the young group, which showed lower vessel formation and maturation capacity of stromal vascular fraction from older animals. Therefore, we expect to witness identical results in the stromal vascular fraction group from younger individuals. Second, the results did not show the discrepancy in adipose persistence rate between the quality and quantity–cultured mononuclear cell (MNC-QQ) group and the stromal vascular fraction group by 7 weeks after injection, which may shadow the future study of MNC-QQ. The MNC-QQ technique requires 1 week of culture in vitro, while stromal vascular, which also promotes fat retention in free fat grafting, barely needs any cell separation or culture. Therefore, we anticipate more data to show the superiority of MNC-QQ. Because MNC-QQ promoted higher vessel density compared with stromal vascular by 7 weeks and a previous study showed grafted fat underwent degeneration, regeneration, and stabilization until 3 months to 1 year or even more,5 we think that it might help to yield positive results if authors enlarge the volume of grafted fat tissue or elongate the observation time to 3 months. Third, we are thankful for the authors’ effort to prove that quality and quantity culture improved the proangiogenic capacity of peripheral blood mononuclear cells; however, we question the efficiency of MNC-QQ to enhance free fat grafting, considering the amount of blood. The experimenters drew 150 ml of venous blood to separate human mononuclear cells. However, since the exact details of the experiments are unknown, we calculate that 150 ml of blood supported only 0.25 g of free fat in about 40 mice [peripheral blood mononuclear cells group (16) + MNC-QQ group (16) + additional testing (8) = 40], which means 15 ml of venous blood promoted the survival of merely 1 g of fat. Patients might hesitate to choose MNC-QQ, especially those who require large-volume fat grafting. Hence, researchers should take into account the dose-response relationship between peripheral blood and grafted fat. DISCLOSURE The authors declare that they have no conflicts of interest to disclose. Ao Fu, M.D.Yiye Ouyang, M.D.Xingyi Du, M.D.Xiaomu Ma, M.D.Chunjun Liu, M.D., Ph.D.Plastic Surgery Hospital (Institute)Peking Union Medical CollegeChinese Academy of Medical SciencesBeijing, People’s Republic of China