In Vitro and In vivo Interaction of Adipose-Derived Stem Cells and Breast Cancer Cells: Is fat grafting safe in post-mastectomy patients?
Hakan Orbay, MD, PhD, Heath J. Charvet, MD, Katharine M. Hinchcliff, MD, Tima Dehghani, BS, Mankushpreet Kaur, BS, David E. Sahar, BS.
University of California Davis, Sacramento, CA, USA.
We investigate the in vitro and in vivo interaction of breast cancer cells (BCCs) and adipose-derived stem cells (ASCs) in an attempt to better understand the clinical risks of fat grafting in post-mastectomy breast reconstruction.
For in vitro study BCCs and ASCs were obtained from the same patient. A homogenous (CD 90-/CD 24+) BCC population was obtained with flowcytometric cell sorting. The effect of ASCs on migration of BCCs was examined using a cell migration assay. In vivo arm of the study was performed using MDA-MB-231 BCCs and patient derived ASCs/fat grafts. BCCs were injected to the 4th mammary gland of female nude mice (n=20) bilaterally as shown in Figure 1A. 1.65x105 BCCs, 1.45x105 ASCs, and 150 µl of unprocessed fat graft were injected in corresponding groups. Tumors were followed with serial digital caliper measurements and examined histologically after 4 weeks.
The percentage of CD 90-/CD 24+ BCCs in initial cell population was 0.61 %. BCCs migrated approximately 10 folds more when co-cultured with ASCs compared to BCC only cultures (p<0.01). Tumor growth rate in group III and group IV was significantly higher than group I (p<0.01) (Figure 1B). Histologically, injected fat grafts were largely replaced by BCCs after 4 weeks.
ASCs significantly increase the in vitro migration of BCCs in co-cultures and in vivo growth of breast cancer xenografts.
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