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Use of Adipose Derived Stem Cells in Head and Neck Oncologic Reconstructive Surgery: Is there Concern?
Mei Sheng, M.D., Ph.D.1, Murali Anbalagan, Ph.D.1, Eduardo A. Lacayo, M.D.2, Ryan K. Jones, B.A.1, Jessica Devay, Ph.D.1, Jeffrey M. Gimble, M.D., Ph.D.3, Paul L. Friedlander, M.D.2, Brian G. Rowan, Ph.D.1, Ernest S. Chiu, MD4.
1Structural and Cellular Biology, Tulane School of Medicine, New Orleans, LA, USA, 2Head & Neck Oncology, Tulane School of Medicine, New Orleans, LA, USA, 3Pennington Biomedical Center, Baton Rouge, LA, USA, 4NYU Langone Medical Center, New York, NY, USA.
PURPOSE: Head and neck cancer (HNC) is the sixth most common malignancy, accounting for >400,000 new cases per year. Following surgical resection and radiation, patients exhibit impaired wound healing, scar contracture, and disfigurement of the head and neck region, often requiring reconstructive surgery. Autologous fat transplantation is one treatment option for post-irradiation wounds. Abdominal fat tissues, which contain adipose-derived stem cells (ASC), are harvested and injected into the affected area. ACS’s can improve and accelerate wound healing, tissue regeneration, and cellular differentiation. However the safety and efficacy of ASC’s and their potential interaction with HNC is unknown. The goal of this study is to investigate the interaction between human ASC’s and HNC squamous cell carcinoma cell lines, CAL-27 and SCC-4, using both in vitro and in vivo approaches.
METHODS: A wound healing “scratch” assay was used to measure HNC cell migration in the presence of ASC conditioned media (CM). 3.0 x 105 CAL-27 HNC cells or 2.0 x 105 SCC-4 HNC cells were cultured in DMEM and 10% fetal bovine serum (FBS) and allowed to adhere for 24 hours. Cultures were incubated with ASC CM following a ‘scratch’ wound, and were cultured for an additional 6 hours for CAL-27 and 16 hours for SCC-4. Photographs of the CAL-27 cultures were taken at 0-16 hours. CAL-27 (3x106 cells) expressing GFP were injected into the flanks of Nude mice, with or without an equal number of ASCs expressing RFP to monitor the effect of ASCs on CAL-27 tumor growth and metastasis after 6 weeks. Tumor volume was monitored by caliper measurement. Metastasis was assessed by visual observation of mouse organs, quantitation of human chromosome 17 DNA by quantitative PCR, and by histological and fluorescent examination of metastatic sites.
RESULTS: In vitro wound healing “scratch” assay demonstrated that ASC CM stimulated CAL-27 migration, causing an 11 ± 5% gap closure at 20% ASC CM, and 14 ± 6% gap closure at 50% CM, compared to 7% gap closure at 0% CM. ASC also stimulated SCC-4 migration causing a 48 ± 9% gap closure at 20% CM, and 44 ± 9%, gap closure at 50% CM, compared to 36% gap closure at 0% CM. Co-injection of ASCs with CAL-27 tumor cells increased primary tumor volume two fold, and increased CAL-27-GFP metastasis to multiple organs. Mouse organs showed presence of CAL-27-GFP and ASC-RFP fluorescence, including overlapping red and green fluorescence at several organ sites.
CONCLUSION:
1. This is the first known study to examine interaction of human ASC's with human Head/Neck Cancer cells and to examine its potential safety concerns.
2. Human ASC's stimulated squamous cell carcinoma migration via a paracrine factor mechanism in an in vitro assay.
3. Human ASC's co-injected with CAL-27 HNC cells increased primary tumor volume and stimulated CAL-27 metastasis to multiple organs.
4. this time, the use of ASC for accelerating wound repair or improving functional and aesthetic outcomes is not recommended in head/neck cancer prone microenvironments until additional scientific studies are confirmed.
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