Ex vivo-expanded autologous adipose tissue-derived stromal cells ensure enhanced fat graft retention in breast augmentation: A randomized controlled clinical trial.

Autologous fat grafting and implant surgery are used for volume restoration in plastic surgery. With the aim of producing a treatment superior to current solutions, we report a randomized, controlled, data assessor-blinded clinical trial comparing fat grafts enriched with ex vivo-expanded autologous adipose-derived stromal cells (ASCs) to nonenriched fat grafts in breast augmentation. The intervention group received ASC-enriched fat grafts (≥20 × 106 viable ex vivo-expanded ASCs per milliliter fat), and the control group received conventional nonenriched fat grafts. Volume retention was measured by magnetic resonance imaging, and clinical photographs were taken simultaneously for outcome evaluation. ASC-enriched fat grafts had significantly higher retention rates (mean = 80.2%) compared with conventional fat grafts (mean = 45.1%). Clinical photos showed statistically significant superior results in the intervention group, assessed by independent clinical experts. These results improve the prospects for using culture-expanded ASCs in both reconstructive and cosmetic volume restoration and make the procedure an attractive alternative to conventional fat grafting and implants. This study is registered at www.ClinicalTrials.gov, number H-16046960.

Cell-Enriched Fat Grafting Improves Graft Retention in a Porcine Model: A Dose-Response Study of Adipose-Derived Stem Cells versus Stromal Vascular Fraction.

BACKGROUND: Cell-enrichment of fat grafts has produced encouraging results, but the optimal concentrations and types of added cells are unknown. The authors investigated the effects of enrichment with various concentrations of ex vivo-expanded adipose-derived stem/stromal cells and stromal vascular fraction on graft retention in a porcine model. METHODS: Adipose-derived stem/stromal cells were culture-expanded, and six fat grafts (30 ml) were prepared for each minipig (n = 13). The authors investigated grafts enriched with 2.5 × 10 to 20 × 10 adipose-derived stem cells/ml and stromal vascular fraction and nonenriched control grafts. Each pig served as its own control. Magnetic resonance imaging was performed immediately after grafting and 120 days postoperatively before the pigs were euthanized, and histologic samples were collected. RESULTS: The authors recorded an enhanced relative graft retention rate of 41 percent in a pool of all cell-enriched grafts compared to the nonenriched control (13.0 percent versus 9.2 percent; p = 0.0045). A comparison of all individual groups showed significantly higher graft retention in the 10 × 10-adipose-derived stem/stromal cells per milliliter group compared with the control group (p = 0.022). No significant differences were observed between the cell-enriched groups (p = 0.66). All fat grafts showed a significantly better resemblance to normal fat tissue in the periphery than in the center (p < 0.009), but no differences in overall graft morphology were observed between groups (p > 0.17). CONCLUSIONS: Cell-enriched fat grafting improved graft retention and was feasible in this porcine model. No significant differences in graft retention were observed among the various adipose-derived stem/stromal cell concentrations or between adipose-derived stem/stromal cell and stromal vascular fraction enrichment. Future studies using this model can help improve understanding of the role of adipose-derived stem/stromal cells in cell-enriched fat grafting.

A Novel Porcine Model for Future Studies of Cell-enriched Fat Grafting.

BACKGROUND: Cell-enriched fat grafting has shown promising results for improving graft survival, although many questions remain unanswered. A large animal model is crucial for bridging the gap between rodent studies and human trials. We present a step-by-step approach in using the Göttingen minipig as a model for future studies of cell-enriched large volume fat grafting. METHODS: Fat grafting was performed as bolus injections and structural fat grafting. Graft retention was assessed by magnetic resonance imaging after 120 days. The stromal vascular fraction (SVF) was isolated from excised fat and liposuctioned fat from different anatomical sites and analyzed. Porcine adipose-derived stem/stromal cells (ASCs) were cultured in different growth supplements, and population doubling time, maximum cell yield, expression of surface markers, and differentiation potential were investigated. RESULTS: Structural fat grafting in the breast and subcutaneous bolus grafting in the abdomen revealed average graft retention of 53.55% and 15.28%, respectively, which are similar to human reports. Liposuction yielded fewer SVF cells than fat excision, and abdominal fat had the most SVF cells/g fat with SVF yields similar to humans. Additionally, we demonstrated that porcine ASCs can be readily isolated and expanded in culture in allogeneic porcine platelet lysate and fetal bovine serum and that the use of 10% porcine platelet lysate or 20% fetal bovine serum resulted in population doubling time, maximum cell yield, surface marker profile, and trilineage differentiation that were comparable with humans. CONCLUSIONS: The Göttingen minipig is a feasible and cost-effective, large animal model for future translational studies of cell-enriched fat grafting.

Avoiding a Systematic Error in Assessing Fat Graft Survival in the Breast with Repeated Magnetic Resonance Imaging.

Several techniques for measuring breast volume (BV) are based on examining the breast on magnetic resonance imaging. However, when techniques designed to measure total BV are used to quantify BV changes, for example, after fat grafting, a systematic error is introduced because BV changes lead to contour alterations of the breast. The volume of the altered breast includes not only the injected volume but also tissue previously surrounding the breast. Therefore, the quantitative difference in BV before and after augmentation will differ from the injected volume. Here, we present a new technique to measure BV changes that compensates for this systematic error by defining the boundaries of the breast to immovable osseous pointers. This approach avoids the misinterpretation of tissue included within the expanded boundaries as graft tissue. This new method of analysis may be a reliable tool for assessing BV changes to determine fat graft retention and may be useful for evaluating and comparing available surgical techniques for breast augmentation and reconstruction using fat grafting.