Chapter 1 of 5 · Fundamentals
Platform rationale
Introduction and rationale for patient-derived GBM tissue platform
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What the experts said
Traditional methods like animal models and cell cultures fall short in replicating the complexity of glioblastoma microenvironment
Patient GBM tissue can closely mimic the microenvironment of glioblastoma and allow testing of therapeutic interventions
The microfluidic chip maintains GBM tissue from patients for 8 days and in some cases 12 days in the lab
GBM tissue is collected during surgery with patient consent, placed in nutrient media immediately, and transferred to lab within one hour
The microfluidic system uses a cylindrical shape with inner tube connected to syringe with nutrient media, with or without treatment, and effluent tube collecting released cytokines
The treatment tested was temozolomide plus protein arginine methylation inhibitors
The Harvard syringe pump delivers nutrient media at a rate of 3 microliters per minute over 8 to 12 days
Effluent containing cytokines is collected every 24 hours and stored at -80°C to maintain cytokine integrity
The RDN Systems protein profiler membrane allows testing of 105 human cytokines in a single membrane in duplicate form
Part of the 105 cytokines detected by protein profiler membrane are validated by ELISA
Data has been collected from 13 patients over 12 days
H&E staining shows GBM tissue cells maintain integrity after 8 days on the chip and also at 12 days
GBM tissue viability in the microfluidic chip shows minimal difference over the first 4 days
After 96 hours (4 days), GBM tissue begins to decrease and change patterns, with more pronounced changes at 12 days
EGF and MMP9 are significantly reduced under the novel treatment (temozolomide plus protein arginine methylation inhibitors) compared to control
Serpin E3-like 1, a cytokine mainly related to colon cancer, is abundant in GBM and increases against treatment, potentially indicating a role in resistance
The microfluidic model is a potential GBM model to test therapeutic interventions and assess effects over 8 to 12 days