Fat Graft Safety after Oncologic Surgery: Addressing the Contradiction between In Vitro and Clinical Studies

Abstract

Background: The authors investigate the in vitro and in vivo interaction of human breast cancer cells and human adipose-derived stem cells to address the controversy on the safety of postmastectomy fat grafting. Methods: The authors co-cultured human adipose-derived stem cells and MDA-MB-231 breast cancer cells in an in vitro cell migration assay to examine the migration of breast cancer cells. In the in vivo arm, the authors injected breast cancer cells (group I), human breast cancer cells plus human adipose-derived stem cells (group II), human breast cancer cells plus human fat graft (group III), and human breast cancer cells plus human fat graft plus human adipose-derived stem cells (group IV) to the mammary fat pads of female nude mice (n = 20). The authors examined the tumors, livers, and lungs histologically after 2 weeks. Results: Migration of breast cancer cells increased significantly when co-cultured with adipose-derived stem cells (p < 0.05). The tumor growth rate in group IV was significantly higher than in groups I and II (p < 0.05). The tumor growth rate in group III was also higher than in groups I and II, but this difference was not statistically significant (p > 0.05). Histologically, there was no liver/lung metastasis at the end of 2 weeks. The vascular density in the tumors from group IV was significantly higher than in other groups (p < 0.01). Conclusion: The injection of breast cancer cells, fat graft, and adipose-derived stem cells together increases breast cancer xenograft growth rates significantly.

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

“…A separate study showed that free fatty acids released by subcutaneous fat inhibit the proliferation of MCF-7 as a possible mechanism [29]. In line with our in vitro results showing no changes in MDA-MB-231 cells' proliferation pattern in co-culture, fat grafting studies in mice showed no significant changes in the MDA-MB-231 tumor volume [22,25]. On the other hand, two independent studies using a transwell paracrine co-culture system showed an increase in the MCF-7 cells' proliferation upon incubation with lipoaspirate [20,21].…”

“…Despite the large number of studies surrounding the topic, the field still lacks a clear direction due to conflicting reports from the variable choices of in vitro and in vivo study models. For example, in vitro studies utilized ASCs, in vitro differentiated adipocytes or floating adipocytes as the co-culture interaction partner of breast cancer cells, and reported the tumorigenic behavior of the breast cancer cells [14,16,20,22]. These interactive studies may not reflect the actual clinical scenario of AFT, where lipoaspirates are injected into tumor beds that may or may not have remnant active tumor cells.…”

“…An important concern pertaining to the use of fat grafts for the post-oncological reconstruction of the breast is the possible aggravation of the remnant breast cancer cells upon interaction with transferred autologous fat in the form of lipoaspirates. Although several clinical and animal studies have demonstrated similar or lower incidences of cancer recurrence from post-oncological reconstruction with fat graft compared to other means of breast reconstruction [1,23,24], there still exist substantial data indicating a pro-oncogenic role of lipoaspirates and adipose-derived stem cells [14,16,20,22]. To the best of our knowledge, the most clinically relevant scenario has yet to be studied, i.e., a direct cell-cell contact interaction between lipoaspirates and breast cancer cells.…”

“…Previous studies have reported conflicting results regarding the role of ASCs in promoting the proliferation and malignant transformation of breast cancer cells [2,[14][15][16]22,25]. We isolated ASCs from the same donors from whom lipoaspirates were obtained and propagated them in vitro.…”

“…However, most studies that suggest ASCs increase tumor progression use co-culture or in vivo models, which is inconsistent with the clinical scenario composed of intact adipose parcels injected into a large tissue bed for breast reconstruction. In addition, most of the studies relied on in vitro differentiated adipocytes or paracrine interactions between cells as experimental models [14,16,17,[20][21][22]. On the other hand, a recent study from our lab demonstrated the oncological safety of lipofilling as part of the surgical platform for breast reconstruction after cancer therapy.…”