Data-driven computational model of 3D glioblastoma spheroid growth: the effect of mesenchymal stem cell integration

Abstract

This thesis presents the development of a biologically informed 3D com- putational model of glioblastoma (GBM) spheroid growth under co-culture conditions with mesenchymal stromal cells (MSCs). It integrates a Cellular Potts framework with reaction-diffusion dynamics and logic-based cell state transitions. Experimental co-culture data analysis revealed that MSCs promoted GBM growth under specific conditions. The model was calibrated to match this am- plification, requiring MSCs to adopt context-dependent pro-tumor behavior. Simulations then reproduced not only growth trends but also spatial features such as nutrient gradients, delayed but accelerated necrosis, and viable rim expansion. These results suggest that MSCs can shape tumor metabolism and struc- ture beyond proliferation alone. The model highlights the importance of context-dependent MSC behavior as a potential therapeutic target and pro- vides a biologically grounded framework for investigating tumor-stroma in- teractions and generating testable hypotheses.

Tato diplomova ́ pra ́ce pr ̌edstavuje vy ́voj biologicky motivovane ́ho 3D vy ́poc ̌etnı ́ho modelu ru ̊stu sfe ́roidu glioblastomu (GBM) v kokultur ̌e s mesenchyma ́lnı ́mi stroma ́lnı ́mi bun ̌kami (MSC). Model kombinuje Cellular Potts model s re- akc ̌ne ̌-difuznı ́dynamikou a pr ̌echody bune ̌c ̌ny ́ch stavu ̊podle loka ́lnı ́ch podmı ́nek a stochasticke ́ rozhodova ́nı ́. Analy ́za experimenta ́lnı ́ch dat z kokultur odhalila, z ̌e MSC podporujı ́ru ̊st GBM za specificky ́ch podmı ́nek. Model byl kalibrova ́n tak, aby odpovı ́dal tomuto zjis ̌te ̌nı ́, pr ̌ic ̌emz ̌ MSC vykazovaly kontextove ̌ za ́visle ́ chova ́nı ́ pod- porujı ́cı ́ ru ̊st na ́doru. Simulace na 'sledne ̌ reprodukovaly nejen ru ̊stove ́ trendy, ale i prostorove ́ charakteristiky, jako jsou nutric ̌nı ́ gradienty, zpoz ̌de ̌na ́, avs ̌ak zrychlena ́ nekro ́za a expanze proliferujı ́cı ́ povrchove ́ vrstvy. Tyto vy 'sledky naznac ̌ujı ́, z ̌e MSC mohou ovlivn ̌ovat na ́dorovy ́ metabolis- mus a strukturu i jiny ́mi mechanismy nez ̌ jen podporou proliferace. Model zdu ̊razn ̌uje vy ́znam kontextove ̌ za ́visle ́ho chova ́nı ́ MSC jako moz ̌ne ́ho tera- peuticke ́ho cı ́le a slouz ̌ı ́ jako biologicky inspirovany ́ na 'stroj pro zkouma ́nı ́ in- terakcı ́ mezi na ́dorem a stromatem a pro generova ́nı ́ testovatelny ́ch hypote ́z.