| Abstract Body | Background
Glioblastoma (GBM) poses a significant therapeutic challenge due to its complex tumour microenvironment. Traditional models often fail to recapitulate the intricate cellular interactions and physiological conditions found in GBM. To address this, we explored the use of microfluidic devices to maintain living GBM tissue ex vivo, enabling real-time analysis of cytokine release patterns.
Aim:
We investigated the cytokine release patterns from patient-derived GBM tissue maintained on a microfluidic platform for up to 8-12 days. The tissue was subjected to a novel drug combination (TMZ + PRMT inhibitor) and compared to untreated controls.
Methods
GBM tissue samples were obtained from patients undergoing surgical resection at Hull Royal Infirmary. The tissue was sliced and incubated within a custom-designed microfluidic chip perfused with nutrient media at a rate of 3 μL/min for up to 12 days . The effluent was collected at 24-hour intervals and analyzed using a Proteome Profiler Human XL Cytokine Array Kit then validated part of the results by ELISA.
Results
From 13 patients (10 primary, 3 recurrent; 6 MGMT-positive, 7 MGMT-negative), the most frequent cytokines detected were Chitinase 3-like 1, IL-8, Osteopontin, and CCL2/MCP-1. A multivariate model identified Time, Gender, and Age as significant factors affecting cytokine levels, with Treatment showing no significant overall effect. However, individual cytokine analysis revealed significant upregulation of Angiopoietin-2, Apolipoprotein A-1, and BDNF, while the treatment significantly downregulated andMMP-9 the VEGF.
Conclusion
This study demonstrates the feasibility of maintaining viable GBM tissue on a microfluidic platform for extended periods. Cytokine analysis revealed dynamic changes in response to treatment, highlighting the potential of this model for studying GBM biology and evaluating therapeutic interventions.
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