The Impact of Human Lipoaspirate and Adipose Tissue-Derived Stem Cells Contact Culture on Breast Cancer Cells: Implications in Breast Reconstruction

Abstract

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.

Bioprinting and Differentiation of Adipose-Derived Stromal Cell Spheroids for a 3D Breast Cancer-Adipose Tissue Model

“…Ongoing studies include investigations into the secretory function of adipocytes as well as tumor cells and the role of lipid metabolism and specific ECM components in tumor cell proliferation and migration, also using modified hydrogel formulations that support migration of the tumor cells. Furthermore, due to its modular design and the possible long-term culture, the presented model may also be utilized to investigate the interaction of ASC-enriched lipografts and breast cancer cells in the context of breast reconstruction in an in vivo-like 3D environment, which is an important aspect to evaluate this treatment in terms of oncological risk [ 67 ].…”

Adipose-Derived Stem Cells in the Treatment of Perianal Fistulas in Crohn’s Disease: Rationale, Clinical Results and Perspectives

“…Among all these clinical trials, no evidence of a potential pro-oncogenic role of ADSCs has been shown despite pre-clinical studies that raised some evidence that adipose stem cells might have a role in the tumor microenvironment as well as in tumor promotion [ 132 , 133 , 134 ]. A recent report demonstrated that human lipoaspirate material had no pro-oncogenic properties in vitro [ 135 ]. However, long term in vivo experiments and follow-up of treated patients are still needed.…”

Adipose-Derived Stem Cell: “Treat or Trick”

“…However, in a recent study carried out by Ejaz et al, (2020), it was found that lipoaspirates and ADSCs did not increase the proliferation rate of breast cancer cells either through paracrine- or contact-dependent interactions [ 33 ]. They stated that a previous study on the effect of ADSCs in increasing tumor progression using co-culturing or an In-vivomodel method was inconsistent with the clinical scenario based on the injection of intact adipose parcels into a large tissue bed for breast reconstruction.…”

“…They stated that a previous study on the effect of ADSCs in increasing tumor progression using co-culturing or an In-vivomodel method was inconsistent with the clinical scenario based on the injection of intact adipose parcels into a large tissue bed for breast reconstruction. Since most of the studies on this topic relied on In-vitro differentiated adipocytes or paracrine interactions between cells as experimental models, Ejaz et al, (2020) used a clinically relevant animal model and reported no increase in tumor size, proliferation, histological grade, or metastatic spread [ 33 ]. Even though their result contrasted with the conclusion of a previous study by Koellenspergers et al, (2017), its positive outcome might become something that scientists could build on in the future to create novel breast cancer treatments.…”