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MSc Thesis Defense: Hanife Kantarcı

Modulation of Glioblastoma Cell Behavior by Monocyte-Derived Macrophages and Frequency-Dependent Attraction on a Microfluidic Chip

 

 

Hanife Kantarcı
Molecular Biology, Genetics and Bioengineering, MSc Thesis, 2025

 

Thesis Jury

Assoc. Prof. Dr. Meltem Elitaş (Thesis Advisor)

Assoc. Prof. Dr. Özlem Kutlu

Assoc. Prof. Dr. Ali Fuat Ergenç

 

 

Date & Time: July 23rd, 2025 –  13.30 PM

Place: FENS 2019

Zoom link: https://sabanciuniv.zoom.us/u/a6vJ1wLy4

Keywords : Glioblastoma Multiforme (GBM), Tumor Microenvironment (TME), Monocyte-Derived Macrophages, Glioma Cell Behavior, Dielectrophoresis (DEP), Microfluidic Chip

 

 

Abstract

 

Glioblastoma Multiforme (GBM) is a highly aggressive and heterogeneous primary brain tumor, marked by rapid proliferation, therapeutic resistance, and complex interactions within the tumor microenvironment (TME). Among the key modulators of the TME are tumor-associated macrophages (TAMs), which play a pivotal role in shaping glioma behavior and influencing treatment outcomes. This thesis investigates the impact of monocyte-derived macrophage phenotypes (M0, M1, and M2) on glioma cell proliferation and migration. THP-1 cells were differentiated into macrophage subtypes via cytokine-driven protocols. Functional assays revealed that M1 macrophages enhanced glioma proliferation while attenuating migratory capacity, whereas M2 macrophages initially suppressed proliferation, followed by increased growth and significantly enhanced wound closure, suggesting a dual-phase modulatory effect.

To enable precise, label-free cellular analysis, a microfluidic platform incorporating dielectrophoresis (DEP) was developed. Computational simulations validated optimal electric field distributions for effective DEP-based manipulation of glioma cells. The DEP buffer was shown to preserve glioma cell viability, supporting its potential use in non-destructive diagnostics. Additionally, impedance spectroscopy confirmed the system’s sensitivity to cellular heterogeneity across different glioma lines. Device performance 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 GBM progression and highlights the promise of DEP-integrated microfluidics for advanced glioma diagnostics and future therapeutic applications.