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Cited by 383D Printing in Biomedical ResearchMicrofluidic and Capillary Electrophoresis ApplicationsCancer Cells and Metastasis

The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.

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

Open access
Bower, Ruth, Green, Victoria L, Kuvshinova, Elena, Kuvshinov, Dmitriy, Karsai, Laszlo, Crank, Stephen T, Stafford, Nicholas D, Greenman, John·2017·Future Science OA
DOI 10.4155/fsoa-2016-0089PMC PMC5481812
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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.

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Crossref · 10.4155/fsoa-2016-0089

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Figures

Figure 1. Schematic diagram showing the parallel nature of the on-chip treatment testing concept. Ex vivo testing of tissue response provides potential for the selection of treatment on an individual patient basis.
Figure 1. Schematic diagram showing the parallel nature of the on-chip treatment testing concept. Ex vivo testing of tissue response provides potential for the selection of treatment on an individual patient basis.CC BY · PubMed Central
Figure 2. Photographs of microfluidic culture device and setup. (A) Device close up including PEEK plastic microport and PDMS-filled PEEK-threaded adaptor. Connected to inlet and outlet ETFE tubing via graphite ferrules. (B) Complete culture setup with syringes containing complete medium attached to a pressure-driven syringe pump for continuous flow to the tissue sample within the device. Effluent was collected in Eppendorf tubes and the devices were maintained in an incubator at 37°C. ETFE: Ethylene tetrafluoroethylene; PDMS: Polydimethylsiloxane; PEEK: Polyether ether ketone.
Figure 2. Photographs of microfluidic culture device and setup. (A) Device close up including PEEK plastic microport and PDMS-filled PEEK-threaded adaptor. Connected to inlet and outlet ETFE tubing via graphite ferrules. (B) Complete culture setup with syringes containing complete medium attached to a pressure-driven syringe pump for continuous flow to the tissue sample within the device. Effluent was collected in Eppendorf tubes and the devices were maintained in an incubator at 37°C. ETFE: Ethylene tetrafluoroethylene; PDMS: Polydimethylsiloxane; PEEK: Polyether ether ketone.CC BY · PubMed Central
Figure 3. Hematoxylin and Eosin-stained 8-µm tissue sections, shown at 100× and 400× magnification. Two representative tumors are shown (n = 15). (A) Laryngeal squamous cell carcinoma, staging T4aN0M0. (B) Transglottic laryngeal squamous cell carcinoma, staging T4N0M0. Each tumor is shown pre- and post-48-h microfluidic culture. The bright pink-stained areas on some of the images depict extracellular keratin (keratin pearls*), arising from the squamous cells. White arrows show infiltrating islands and cords of tumor cells. Tumor area showing orientation of cell maturation is circled in white. Pale stromal areas with inflammatory cells are circled in yellow. Intact basement membrane is shown by yellow arrows.
Figure 3. Hematoxylin and Eosin-stained 8-µm tissue sections, shown at 100× and 400× magnification. Two representative tumors are shown (n = 15). (A) Laryngeal squamous cell carcinoma, staging T4aN0M0. (B) Transglottic laryngeal squamous cell carcinoma, staging T4N0M0. Each tumor is shown pre- and post-48-h microfluidic culture. The bright pink-stained areas on some of the images depict extracellular keratin (keratin pearls*), arising from the squamous cells. White arrows show infiltrating islands and cords of tumor cells. Tumor area showing orientation of cell maturation is circled in white. Pale stromal areas with inflammatory cells are circled in yellow. Intact basement membrane is shown by yellow arrows.CC BY · PubMed Central
Figure 4. Viability, cell death and proliferation analysis of single cell suspensions from dispersed tumor tissue before and after microfluidic culture. (A) Percentage viability of cell population by trypan blue exclusion (n = 15). (B) Percentage cell death by PI staining and flow cytometry from 10,000 events (n = 8). (C) Proliferation (MTS assay) of cell suspensions following overnight culture quantified by absorbance of colored formazan product at 492 nm and normalized per milligram of tissue (n = 7). Mean + SEM. PI: Propidium iodide.
Figure 4. Viability, cell death and proliferation analysis of single cell suspensions from dispersed tumor tissue before and after microfluidic culture. (A) Percentage viability of cell population by trypan blue exclusion (n = 15). (B) Percentage cell death by PI staining and flow cytometry from 10,000 events (n = 8). (C) Proliferation (MTS assay) of cell suspensions following overnight culture quantified by absorbance of colored formazan product at 492 nm and normalized per milligram of tissue (n = 7). Mean + SEM. PI: Propidium iodide.CC BY · PubMed Central
Figure 5. Computer simulation of fluid flow and velocity field in the microfluidic culture device. (A) Streamlines and velocity vectors of laminar fluid flow in the device. Labels show inlet, outlet and tissue sample location. (B) Velocity magnitude of the flow within the device. Color legend explains value of the velocity along the channel and the treatment chamber (m/s); thus, the maximum of the velocity equals 1.5 × 10-3 m/s or 1.5 mm/s.
Figure 5. Computer simulation of fluid flow and velocity field in the microfluidic culture device. (A) Streamlines and velocity vectors of laminar fluid flow in the device. Labels show inlet, outlet and tissue sample location. (B) Velocity magnitude of the flow within the device. Color legend explains value of the velocity along the channel and the treatment chamber (m/s); thus, the maximum of the velocity equals 1.5 × 10-3 m/s or 1.5 mm/s.CC BY · PubMed Central
Figure 6. Computer simulation of fluid flow in the microfluidic tissue culture device, with tissue sample tilted 10° due to the flow pressure. (A) Streamlines and velocity vectors of laminar fluid flow in the device. Labels show inlet, outlet and tissue sample location. (B) Velocity magnitude of the flow within the device. Color legend explains value of the velocity along the channel and the treatment chamber (m/s); thus, the maximum of the velocity equals 1.5 × 10-3 m/s or 1.5 mm/s.
Figure 6. Computer simulation of fluid flow in the microfluidic tissue culture device, with tissue sample tilted 10° due to the flow pressure. (A) Streamlines and velocity vectors of laminar fluid flow in the device. Labels show inlet, outlet and tissue sample location. (B) Velocity magnitude of the flow within the device. Color legend explains value of the velocity along the channel and the treatment chamber (m/s); thus, the maximum of the velocity equals 1.5 × 10-3 m/s or 1.5 mm/s.CC BY · PubMed Central
Figure 7. Comparative analysis of the velocity magnitude and Reynolds number of the flow along the sample. Point placement along the sample for further analysis.
Figure 7. Comparative analysis of the velocity magnitude and Reynolds number of the flow along the sample. Point placement along the sample for further analysis.CC BY · PubMed Central

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Citations

Cites

Research works printed but not linked: 1

  1. Dawson A, Green V, Bower R, Greenman J. Microfluidics: towards personalised medicine in cancer therapy. Drug Target Rev. 3, 12–17 (2016).

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Metadata

Authors
Bower, R., Green, V. L., Kuvshinova, E., Kuvshinov, D., Karsai, L., Crank, S. T., Stafford, N. D., & Greenman, J.
Affiliations
  • University of Hull (GB)
  • University of Sheffield (GB)
  • Hull Royal Infirmary (GB)
Corresponding author
Bower, Ruth
ORCID
Venue
Future Science OA
Publisher
Informa UK Limited
Published
2017-03-07
Volume
3
Issue
2
Pages
FSO174-FSO174
ISSN
2056-5623 (ISSN-L)
DOI
10.4155/fsoa-2016-0089
PMC
PMC5481812
OpenAlex
W2593991334
Cited by
38
References
52
Citations by year
2026: 4 · 2025: 4 · 2024: 1 · 2023: 7 · 2022: 3 · 2021: 8 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 1
FWCI
1.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Future Science OA (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repository@Hull (Worktribe) (University of Hull) (acceptedVersion, other-oa)
  • Repository@Hull (Worktribe) (University of Hull) (submittedVersion, cc-by)
Funders
  • University of Hull
  • National Centre for the Replacement, Refinement and Reduction of Animals in Research (G1100600/1)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
head and neck squamous cell carcinoma, personalized medicine, drug response monitoring, tumor viability, computational fluid dynamics

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