Commentary on: Prospective 1-Year Follow-Up Study of Breast Augmentation by Cell-Assisted Lipotransfer.

A large body of experimental evidence supports the positive effect that supplementing standard breast augmentation techniques with adipose-derived stem cells (ASCs) has on fat graft survival; however, several clinical studies, including the study by Jung et al. have found that employing ASCs during breast augmentations has limited therapeutic benefit. How can we explain this discrepancy in the literature on the use of ASCs during breast augmentation? We encountered a similar discrepancy in the literature several years ago. One study found that recombinant tissue factor pathway inhibitor eliminated the thrombogenicity of microvascular anastomoses in the laboratory, but a multicenter, prospective, double-blinded, randomized controlled clinical trial failed to demonstrate that recombinant tissue factor pathway inhibitor substantially improved free flap survival rates. In a previously published article, we focused on anastomosis as the most critical requirement for free flaps survival, but eventually realized that the clinical fate of the flap was often sealed by many other factors. The successful outcome of complex procedures such as large-volume fat grafting and free flap surgery depends on multiple, linked factors, and the weakest link in the series of factors determines the outcome of the procedure. In previously published research, we identified the graft as the most critical aspect of a large-volume fat grafting procedure, when, in fact, the clinical outcome of such procedures actually depends on many other limiting steps. To elaborate on these steps, we compared a surgeon performing a fat grafting procedure to a farmer planting seeds in a field. The success of the procedure depends on four “S”s – the seeds (the graft), the soil (the recipient site), the sowing technique (the surgical craftsmanship), and the support (the aftercare of the graft site and the patient). Perfectly optimizing one of these factors does not compensate for another factor being suboptimal. Success depends on optimization of these four factors. Once all factors are optimized, a specific graft-torecipient interaction has to occur in order for revascularization of the graft to occur. This interaction can be represented by the following equation: G+R=RG. In this equation, the survival of a free fat graft (G) depends on its interaction with the recipient tissue (R) to yield a revascularized, surviving graft (RG). This interaction has a specific stoichiometry. Quadrupling G or enhancing its quality without altering R will not yield better RG. We have previously showed that, in large-volume fat grafting procedures, RG augmentation is strongly correlated with the expansion of R, and enlarging R is linearly related to better RG, regardless of the number of G. This suggests that, in breast augmentations, the recipient site is the limiting factor in fat graft revascularization. Utilizing ASCs as a way of improving large-volume fat grafting is as ineffectual as adding more horsepower to a car stuck in heavy traffic. Traffic has to improve before more horsepower can make a difference. Similarly, the recipient site has to be improved before optimizing the quality or the volume of the fat graft can make a difference. Jung et al. acknowledge that the tighter connective tissues of nulliparous women are less able to accommodate large