Evaluation of the ex vivo Effects of Tamoxifen on Adipose-Derived Stem Cells: A Pilot Study

Abstract

Autologous fat grafting (AFG) is a safe and minimally invasive procedure to correct soft tissue defects. The benefit of AFG is attributed to adipose-derived stem cells (ASCs) in fat tissue graft. This technique is useful also in patients undergoing reconstructive surgery following quadrantectomy for breast cancer. However, these patients are frequently treated with tamoxifen. We evaluated the ex vivo effects of tamoxifen on ASCs to understand if cellular functions of ASCs are affected. We selected 24 female patients; 10 of which were breast cancer patients treated with quadrantectomy and tamoxifen. As control group, we selected 14 healthy female subjects (9 premenopausal and 5 menopausal). We found that tamoxifen has no effect on cellular proliferation, VEGF secretion or apoptosis of ASCs. The gene expression assessment demonstrated no impairment in differentiation capacity of ASCs. Our results showed that tamoxifen has no effect on cellular functions of ASCs for the first time in an ex vivo single-center study.

Influence of Tamoxifen on Different Biological Pathways in Tumorigenesis and Transformation in Adipose-Derived Stem Cells, Mammary Cells and Mammary Carcinoma Cell Lines—An In Vitro Study

“…On the other hand, further studies showed controversial results. In contrast to the present results, it was postulated that tamoxifen does not affect cellular proliferation, vascular endothelial growth factor secretion and apoptosis of ASC [ 42 ]. Furthermore, the gene expression assessment demonstrated no impairment in the differentiation capacity of ASC after tamoxifen treatment [ 42 ].…”

“…In contrast to the present results, it was postulated that tamoxifen does not affect cellular proliferation, vascular endothelial growth factor secretion and apoptosis of ASC [ 42 ]. Furthermore, the gene expression assessment demonstrated no impairment in the differentiation capacity of ASC after tamoxifen treatment [ 42 ]. The results of the study at hand are another keystone to depict the controversial facts about ASC and parallel tamoxifen treatment.…”

“…Other studies confirmed these results, showing that tamoxifen inhibits ASC proliferation and induces apoptosis in a dose and time-dependent manner [ 41 ]. On the other hand, Boemi et al pointed out that the concentration of tamoxifen is much lower in fat than in other parts of the body and claimed that tamoxifen does not significantly affect cellular functions and apoptosis rates [ 42 ]. However, the effect of tamoxifen on the gene expression of ASC involved in fat graft survival, tumorigenesis and the transition of mammary carcinoma cells has not been analyzed yet.…”

Breast fat grafting and cancer: a systematic review of the science behind enhancements and concerns

“…When ex-vivo breast cancer cells were co-cultured with ADSCs-enriched medium and tamoxifen, tamoxifen treatment simultaneously reduced the differentiation of ADSCs into adipogenic and osteogenic cells, while also inhibiting their proliferation in a dose-dependent manner ( 12 ). While these findings contradict the results of a study by Boemi et al , which compared ADSCs from women with breast cancer who were taking tamoxifen to ADSCs from menopausal women, suggesting that tamoxifen (20 mg/day) had no effect on ADSC apoptosis compared to the control group ( 13 ). MDA-MB-231 and ADSCs underwent treatment with paclitaxel (1.0 µM) or low-dose paclitaxel (0.1 µM) in combination with a histone deacetylase inhibitor, providing additional insights into the interaction between ADSCs and chemotherapy.…”

Disulfiram Improves Fat Graft Retention by Modulating Macrophage Polarization With Inhibition of NLRP3 Inflammasome-Mediated Pyroptosis

“…Autologous fat grafting is widely utilized for soft tissue filling and reconstructive surgery because of its good biocompatibility and minimal invasiveness. 1 , 2 However, the poor retention rate of fat grafts is a pressing problem that needs to be addressed. 3 Grafted fat tissue must be revascularized as soon as possible in the recipient area to achieve a satisfactory retention rate.…”