Modulation Of Glioblastoma Cell Behavior By Monocyte-Derived Macrophages And Frequency-Dependent Attraction On A Microfluidıc Chip

Glioblastoma Multiforme (GBM) is a highly aggressive and heterogeneous primarybrain tumor, marked by rapid proliferation, therapeutic resistance, and complexinteractions within the tumor microenvironment (TME). Among the key modulatorsof the TME are tumor-associated macrophages (TAMs), which play a pivotalrole in shaping glioma behavior and influencing treatment outcomes. This thesisinvestigates the impact of monocyte-derived macrophage phenotypes (M0, M1, andM2) on glioma cell proliferation and migration. THP-1 cells were differentiatedinto macrophage subtypes via cytokine-driven protocols. Functional assays revealedthat M1 macrophages enhanced glioma proliferation while attenuating migratorycapacity, whereas M2 macrophages initially suppressed proliferation, followed by increasedgrowth and significantly enhanced wound closure, suggesting a dual-phasemodulatory effect.To enable precise, label-free cellular analysis, a microfluidic platform incorporatingdielectrophoresis (DEP) was developed. Computational simulations validated optimalelectric field distributions for effective DEP-based manipulation of glioma cells.The DEP buffer was shown to preserve glioma cell viability, supporting its potentialuse in non-destructive diagnostics. Additionally, impedance spectroscopy confirmedthe system’s sensitivity to cellular heterogeneity across different glioma lines. Deviceperformance was validated using U-87 glioma cells, demonstrating reliable cell behavior tracking and morphological assessment.Overall, the study underscores the regulatory role of macrophage subtypes in GBMprogression and highlights the promise of DEP-integrated microfluidics for advancedglioma diagnostics and future therapeutic applications.