Ex vivo culture of head and neck cancer explants in cell sheet for testing chemotherapeutic sensitivity

Purpose

: Tumor explant culture systems can mimic the in vivo tumor microenvironment, proposing as a substitute for preclinical studies for prediction of individual treatment response. Therefore, our study evaluated the potential usefulness of ex vivo tumor explants culture assembled into the cell sheets by anticancer drug screening in patients with head and neck squamous cell carcinoma (HNSCC).

Methods

: Our model included tumor explants incorporated into cell sheet composing of epithelium and subepithelial stroma using tumor and mucosal samples obtained from the HNSCC patients who underwent surgery. Cell growth, viability, and hypoxia were measured by cell counting kit-8, live/dead assay, propidium iodide, and LOX-1 staining, and were compared among the different treatment groups with vehicle, cisplatin or docetaxel.

Results

: Tumor explants stably survived in the cell sheet over 10 days after explantation, whereas most of the explants in non-matrix culture became nonviable within 5–8 days with the significant daily decrease of viability. The live tissue areas of tumor explants in the cell sheet maintained over 30 days without significant changes although hypoxic cell areas gradually increased up to 5 days. Tissue viability and live cancer tissue areas significantly decreased after the treatment of cisplatin or docetaxel in the dose and time-dependent manners.

Conclusion

: Our cell sheet-based tumor explants model might be applied to the reliable ex vivo screening for anticancer chemotherapeutics for HNSCC.