Plastic Surgery Research Council
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PSRC 60th Annual Meeting
Program and Abstracts

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Human Adipose Tissue-Derived Stromal/Stem Cells Promote Migration and Early Metastasis of Head & Neck Cancer Xenografts
Walter J. Joseph, III, BS1, Eduardo A. Lacayo, MD2, Mei Sheng, MD, PhD2, Muralidharan Anbalagan, PhD2, Jeffrey M. Gimble, MD, PhD3, Ryan K. Jones, MA2, Paul L. Friedlander, MD2, Brian G. Rowan, PhD2, Ernest S. Chiu, MD1.
1NYU Langone Medical Center, New York, NY, USA, 2Tulane University School of Medicine, New Orleans, LA, USA, 3Louisiana State University, Baton Rouge, LA, USA.

PURPOSE: Fat grafting has become a popular reconstructive adjunct for repair of post-surgical/post-radiation defects after head/neck cancer resection. With graft necrosis and resorption being a controversial issue, fat graft supplementation with adipose tissue-derived stromal/stem cells (ASCs) has been proposed to improve graft viability and efficacy. However, the impact of ASCs on head/neck cancer cells is unknown.
METHODS: Human Cal-27 and SCC-4 head/neck cancer cells were co-cultured with human ASCs, or treated with ASC conditioned medium (CM). Cancer cell growth and migration were assessed by MTT viability assay, cell count, and the scratch/wound healing assay in vitro. Co-injection of Cal-27/GFP cells and ASCs into the flank of NUDE mice was used to assess ASC effect on tumor growth/morphology via tumor fluorescence and H&E staining. Quantification of human chromosome 17 DNA in mouse organs assessed ASCs effects on micrometastasis. Primary tumors were evaluated for markers of epithelial-to-mesenchymal transition, matrix metalloproteinases, and angiogenesis by immunohistochemistry.
RESULTS: Co-culture of Cal-27 or SCC-4 cells with ASCs or ASC CM had no effect on cell growth in vitro. However, ASC CM stimulated Cal-27 and SCC-4 migration. Co-injection of ASCs with Cal-27 cells did not affect tumor volume at six weeks. ASC/RFP cells were viable and well integrated with Cal-27/GFP cells in the tumors. Co-injection with ASC/RFP cells resulted in increased MMP2, MMP9, IL-8, and microvessel density, as well as increased Cal-27 micrometastasis to the brain.
CONCLUSION: Human ASCs did not alter the growth of human head/neck cancer cells or tumor xenografts, but did stimulate migration and early micrometastasis to the mouse brain. As such, the applied use of ASCs for supplementation of fat grafts for reconstruction after head & neck cancer surgery should be approached with caution until further studies are undertaken to better elucidate the impact of ASCs on head & neck cancer metastasis.


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