Fat grafting popularity continues to rise among plastic surgeons. As a soft tissue filler, adipose tissue had many desirable attributes: it is easy to obtain, autologous, and may reintegrate into recipient sites. However, fat grafting is clinically plagued by unpredictable resorption rates, thus there is much interest in optimizing the procedure of fat grafting for consistent graft volumes. Fat harvesting, a part of fat transfer surgery, involves the removal of adipose tissue from the donor site. Different harvest procedures, such as whole fat excision or liposuction cannulas, result in a range of fat particle volumes, which may play a role in the cellular stability of grafts. The ideal harvesting technique and fat particle diameter is not currently known. This study aims to review the literature on the impact of fat particle size and clinical fat grafting outcomes, to present overarching conclusions, and to provide future directions for study. Current evidence supports excisional methods and larg...

Background: Clinical outcomes suggest that postoncologic reconstruction with fat grafting yields cumulative incidence curves of recurrence comparable to those of other breast reconstruction procedures; however, results from experimental research studies suggest that adipose stem cells can stimulate cancer growth. In this study, a novel animal model of residual cancer was developed in mouse mammary pads to test whether lipofilling impacts the probability of locoregional recurrence of breast cancer after breast conserving surgery. Methods: Mammary fat pads of female NOD-SCID gamma mice were each injected with MCF-7 cells in Matrigel. Tumors were allowed to engraft for 2 weeks, after which time either sterile saline (n = 20) or human fat graft (n = 20) was injected adjacent to tumor sites. After 8 weeks, tumors were assessed for volume measurement, histologic grade, Ki67 positivity, and metastatic spread. Results: Animals receiving lipofilling after tumor cell engraftment had lower tumor volume and mass (p = 0.046 and p = 0.038, respectively). Macroscopic invasion was higher in the saline group. Histologic grade was not significantly different in the two groups (p = 0.17). Ki67 proliferation index was lower in tumors surrounded by fat graft (p = 0.01). No metastatic lesion was identified in any animal. Conclusions: Adipose transfer for breast reconstruction performed in the setting of residual breast tumor in a clinically relevant animal model did not increase tumor size, proliferation, histologic grade, or metastatic spread. This study supports the oncologic safety of lipofilling as part of the surgical platform for breast reconstruction after cancer therapy.

Background: Autologous fat transfer in the form of lipoaspirates for the reconstruction of the breast after breast cancer surgery is a commonly used procedure in plastic surgery. However, concerns regarding the oncologic risk of nutrient-rich fat tissue are widely debated. Previous studies have primarily focused on studying the interaction between adipose-derived stem cells (ASCs) and breast cancer cells. Methods: In this study, we performed a comprehensive analysis of the paracrine- and contact-based interactions between lipoaspirates, ASCs and breast cancer cell lines. An inverted flask culture method was used to study the contact-based interaction between lipoaspirates and breast cancer cells, while GFP-expressing breast cancer cell lines were generated to study the cell–cell contact interaction with ASCs. Three different human breast cancer cell lines, MCF-7, MDA-MB-231 and BT-474, were studied. We analyzed the impact of these interactions on the proliferation, cell cycle and epithelial-to-mesenchymal (EMT) transition of the breast cancer cells. Results: Our results revealed that both lipoaspirates and ASCs do not increase the proliferation rate of the breast cancer cells either through paracrine- or contact-dependent interactions. We observed that lipoaspirates selectively inhibit the proliferation of MCF-7 cells in contact co-culture, driven by the retinoblastoma (Rb) protein activity mediating cell cycle arrest. Additionally, ASCs inhibited MDA-MB-231 breast cancer cell proliferation in cell–cell contact-dependent interactions. Quantitative real-time PCR revealed no significant increase in the EMT-related genes in breast cancer cells upon co-culture with ASCs. Conclusion: In conclusion, this study provides evidence of the non-oncogenic character of lipoaspirates and supports the safety of clinical fat grafting in breast reconstruction after oncological surgical procedures. In vivo studies in appropriate animal models and long-term post-operative clinical data from patients are essential to reach the final safety recommendations.

PEGylated-l-asparaginase (PEG-ASNase) is a chemotherapeutic agent used to treat pediatric acute lymphoblastic leukemia (ALL). Its use is avoided in adults due to its high risk of liver injury including hepatic steatosis, with obesity and older age considered risk factors of the injury. Our study aims to elucidate the mechanism of PEG-ASNase-induced liver injury. Mice received 1500 U/kg of PEG-ASNase and were sacrificed 1, 3, 5, and 7 days after drug administration. Liver triglycerides were quantified, and plasma bilirubin, ALT, AST, and non-esterified fatty acids (NEFA) were measured. The mRNA and protein levels of genes involved in hepatic fatty acid synthesis, β-oxidation, very low-density lipoprotein (VLDL) secretion, and white adipose tissue (WAT) lipolysis were determined. Mice developed hepatic steatosis after PEG-ASNase, which associated with increases in bilirubin, ALT, and AST. The hepatic genes Ppara, Lcad/Mcad, Hadhb, Apob100, and Mttp were upregulated, and Srebp-1c and Fas were downregulated after PEG-ASNase. Increased plasma NEFA, WAT loss, and adipose tissue lipolysis were also observed after PEG-ASNase. Furthermore, we found that PEG-ASNase-induced liver injury was exacerbated in obese and aged mice, consistent with clinical studies of ASNase-induced liver injury. Our data suggest that PEG-ASNase-induced liver injury is due to drug-induced lipolysis and lipid redistribution to the liver.

Background: Animal models are often used to assess interventions that might improve fat grafting outcomes; however, there is great variability in the models. The authors sought to determine the predictive value of the immunocompromised mouse model for fat grafting so that experiments could be standardized and optimized. Methods: Human lipoaspirate injections at different volumes and time points were assessed in a nude mouse model and compared with control injections of nonviable fat. Volume retention and explant histologic score were compared. In a separate study, interanimal reproducibility was determined by implanting a highly consistent hydrogel and measuring variability in volume retention. Results: Injection volume significantly affects adipose resorption kinetics at 6 and 12 weeks. Masson trichrome staining revealed that macrophages were unable to infiltrate large (1 ml) grafts, and oil cysts were not absorbed by 18 weeks, which interfered with interpretation of volume retention data. Nonviable tissue was resorbed when grafts were 0.3 ml, and quantification of graft histologic viability correlated well with graft retention at all study time points. Interanimal variability was measured to be 8.44 percent of the mean retention volume for small graft volumes. Conclusions: Human fat graft retention in the immunodeficient mouse correlates with graft viability in small, 0.3-ml-volume grafts. However, centralized oil cysts in nonviable 1.0-ml grafts were not resorbed by 18 weeks and thus volume measurements were confounded and not significantly different from viable samples. In addition, tissue injury scores increased in initially healthy fat grafts at 18 weeks, possibly because of a delayed immune reaction.

Autologous fat grafting is an important surgical technique in aesthetic and reconstructive procedures. Fat grafting for breast reconstruction is now an established procedure for adding volume and improving cutaneous pliability; it can be used independently to replace more invasive flap procedures or implants, or as an adjunct for smaller volume supplementation. The breadth of applications in the breast necessitates diversity in technique and approach, and while there is no universally agreed-upon protocol, basic principles have guided the evolution of some commonly adopted tenets. Broadly, fat grafting outcomes are highly favorable but dependent on patient and procedure factors, requiring learned patient selection and expertise in recipient site assessment. Common complications from fat grafting, such as fat necrosis and the development of nodules, are particularly troublesome for post-oncologic patients, requiring considerable pre-surgical consultation for patient education and managing expectations. In addition to volume and contour augmentation, fat grafting has additional beneficial effects that have recently drawn increased attention including pain reduction from implant capsular contracture or post-mastectomy pain syndrome, improved skin quality and reduced fibrosis following radiation, and possible anti-tumorigenic effects. New developments in clinical fat grafting research that are promising include the use of adipose progenitor cells admixed with lipoaspirate for improved volume retention or alternative biologics such as platelet-rich plasma. Preclinically, research towards safe and effective regenerative medicine approaches is actively underway, with the ultimate goal of achieving predictable and increased graft retention, reducing the number of required surgical procedures and enabling on-table results to reflect procedure outcomes.