Table 3.
Author | Aim | Drug Stimulant | Culture Model Design and Components | Analytic Outputs | Main Findings | |||
---|---|---|---|---|---|---|---|---|
Single vs. Multicellular Cultures | Primary vs. Cell Lines | 2D vs. 3D Geometry | Hypoxic Cues | |||||
Hattersley et al. (49) | A dynamic culture method as chemotherapy screening platform | -5-FU -Cisplatin |
Single |
Primary:
Patient-derived H&N squamous cell carcinoma Cell lines: -NS |
2D:
Unexposed control Dynamic flow 3D: Multimicro channels Dynamic flow Syringe pump |
NS | -H&E staining -Lactose dehydrogenase release -WST-1 metabolism -Trypan blue -Cytochrome C analysis |
-Preclinical model for personalized medicine and testing -H&E staining showed the retention of multilayer tissue strata -Combination therapy presented higher levels of cytochrome C compared to untreated control |
Riley et al. (91) | A dynamic culture method as drug screening platform | -Etoposide (topoisomerase II inhibitor) -SP600125 (JNK inhibitor) |
Single |
Primary:
Human thyroid tissue samples Cell lines: -NS |
2D:
Unexposed control Dynamic flow 3D: Tissue chamber Dynamic flow Syringe pump |
NS | -Hematoxylin and eosin -Flow cytometry -Trypan blue -Immunohistochemistry staining -Functional analysis - Lactose dehydrogenase release -TUNEL assay -Immunoblot analysis |
-Preclinical model for personalized medicine and testing -H&E staining showed the retention of multilayer tissue strata -Thyroid biopsies were considered functional due to the production of T4 during the culture period -Increased apoptosis on thyroid samples after the perfusion of both drugs in comparison to untreated control |
Al-Samadi et al. (92) | A dynamic culture method as drug screening platform | -PDL1 antibody -IDO1 inhibitor |
Single |
Primary:
Primary H&N squamous cell carcinomas, T cells, B cells, NK cells, monocytes, and dendritic cells Cell lines: -HSC-3 |
2D:
Unexposed control Dynamic flow 3D: Chambers coated with ECM substitute Dynamic flow Unspecified pump |
NS | -Migration assay -Immunofluorescence staining - CellTiter 96® Proliferation Assay -Cell Trace kit |
-Preclinical organotypic model for personalized medicine and testing -IDO 1 inhibitor influences immune cell migration to cancer cells -Therapy response was reported to be patient dependent |
Bower et al. (94) | A dynamic culture method as maintenance platform | NS | Single |
Primary:
Human biopsies of laryngeal, oropharyngeal, or oral cavity tumors staged at T2–T4 Cell lines: -NS |
2D:
Unexposed control Dynamic flow 3D: Biopsy chamber Dynamic flow Syringe pump |
NS | -H&E staining -Trypan blue -Flow cytometry -MTS proliferation assay |
-Patient-derived samples were viable for 48 h after placement in the microfluidic chip -No significance difference concerning the average proliferation of samples pre- and postcultured in the chip |
Lugo-Cintrón et al. (95) | A dynamic culture method as angiogenesis platform | NS | Two-culture |
Primary:
Human tubular lymphatic vessels and cancer-associated fibroblasts Cell lines: -HLEC2500 -HOrF2640 |
2D:
Unexposed control Dynamic flow 3D: Collagen hydrogel adhesion chamber Dynamic flow Syringe pump |
NS | -H&E staining -Immunofluorescence staining -Immunohistochemistry staining -Proliferation assay -Migration and permeability assay -RT-qPCR -Multiphoton microscopy |
-Preclinical organotypic model for personalized medicine and testing -Cancer-associated fibroblasts increased the gene expression of prolymphangiogenic factors in the lymphatic-like vessels |
Sharafeldin et al. (96) | A dynamic culture method as biomarker detection platform | NS | Single |
Primary:
NS Cell lines: -HN12 -HN13 -HN30 -CAL-27 |
2D:
Subtract biomarker control signal 3D: Sonic-assisted chemical lysis chambers Dynamic flow peristaltic micropump |
NS | -Biomarker quantification (desmoglein 3, VEGF-A,VEGF-C, β-Tub) | -Biomarker detection model for cancer metastasis diagnostic -Limit of detection was below 0.20 fg/ml of the analyzed analyte in 20-min evaluation |
Jin et al. (103) | A dynamic culture method as a chemotherapy screening platform | -Paclitaxel -Cisplatin -5-FU |
Two-culture |
Primary:
Patient-derived tumor cells from squamous cell carcinoma and salivary gland adenoid cystic carcinoma Cell lines: -ACC-M -UM-SCC-6 -HUVEC |
2D:
NS 3D: Transwell-like channels -Bottom chambers coated with an ECM substitute Dynamic flow Double syringe pump |
NS | -Hoechst 33342 and propidium iodide -Immunofluorescence staining |
-Preclinical organotypic model for personalized medicine and testing -High concentration of drugs did not provide a therapeutic effect as HUVEC cells were killed. A lower concentration was recommended to provide a therapy to kill cancer cells (over 50% apoptosis) and low HUVEC cytotoxicity (over 50% viability) -Therapy response was reported to be patient dependent concerning different low drug concentrations |
NS, not studied.