Maintenance of Head and Neck Tumor On-Chip: Gateway to Personalized Treatment?

Abstract

Aim:Head and neck squamous cell carcinomas (HNSCC) are solid tumors with low overall survival (40–60%). In a move toward personalized medicine, maintenance of tumor biopsies in microfluidic tissue culture devices is being developed.Methodology/results:HNSCC (n = 15) was dissected (5–10 mg) and either analyzed immediately or cultured in a microfluidic device (37°C) for 48 h. No difference was observed in morphology between pre- and postculture specimens. Dissociated samples were analyzed using trypan blue exclusion (viability), propidium iodide flow cytometry (death) and MTS assay (proliferation) with no significant difference observed highlighting tissue maintenance. Computational fluid dynamics showed laminar flow within the system.Conclusion:The microfluidic culture system successfully maintained HNSCC for 48 h, the culture system will allow testing of different treatment modalities with response monitoring.

A patient tumour-on-a-chip system for personalised investigation of radiotherapy based treatment regimens

“…Maintenance of HNSCC PCTS within on-chip devices is in agreement with and extends previous studies 21,24,26,27,40,41 . In the first part of the work, tissue slices were dissociated to allow viability of cells immediately following surgical resection compared with those from tissue after 68 hours of culture on the on-chip platform.…”

“…Similarly, no significant difference in percentage cell death, as measured by PI uptake, was observed between the dissociated tumour cells before, 73.7% (±5.9) and after, 71.5% (±4.8) the 68-hour maintenance period. The concordance observed between viability (Trypan blue) and cell death (PI) results is in agreement with previous studies which utilised the same mechanical and enzymatic dissociation methods to assess the viability of HNSCC tumour samples before and following maintenance in a microfluidic culture device, for 48 hours, from a 5–10 mg piece of tissue 26 . A similar mechanical and enzymatic dissociation and flow cytometry approach was undertaken by Astolfi et al .…”

“…Dulbecco’s Modified Eagle’s Medium (DMEM, Lonza, Slough, UK) was supplemented as previously described 26 , loaded into a 10 ml syringe and connected to the 2-part adapter and ETFE tubing via a 0.22 µM filter (Millipore, Watford, UK). PCTS were loaded into the tissue well on top of a 70 µm nylon membrane (BD, Oxford, UK) before assembly of the device.…”

“…2 and Supplementary Fig. S1) is described that successfully maintains precision cut tumour slices (PCTS) in a viable state, mimicking in vivo microvascular flow 26,27 to develop a highly reproducible and easy to use unit. A bespoke irradiation system accommodating the tumour-on-a-chip device has also been developed and characterised for highly-controlled irradiation, which can simulate the clinical dose regimen.…”

Microfluidics for interrogating live intact tissues

“…Different groups have addressed the mass transport challenges that slices and biopsies face when placed in a microfluidic environment. A team led by Greenman and Haswell used their previously developed Y-shaped glass device for the interrogation of liver tissue biopsies 54 to test the responses of human head and neck squamous cell carcinoma (HNSCC) tumor biopsies to the chemotherapy drugs cisplatin and 5-fluorouracil 72 , 73 . They found no loss of viability for 48 h and that the combination of both therapies was the most effective at causing cell death.…”