UNDERSTANDING GLIOBLASTOMA INVASION USING 3D BRAIN ORGANOIDS

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor that has a poor prognosis due to tumor recurrence and lack of effective treatment options. In order to address this challenge, we developed a novel 3D in vitro model of GBM that incorporates a co-culture of human iPSC-derived brain organoids with patient-derived GBM cells and its tumor microenvironment components.
To establish this model, we genetically engineered patient derived GBM cells with a secreted luciferase construct bound to an RFP reporter to monitor live cell survival following different therapeutic treatments. The cells were then co-cultured with iPSC-derived brain organoids, and over a period of 15-40 days, both cell lines invaded and grew extensively into the organoid. Subsequently, the 3D Glio-organoids were treated with the standard of care therapeutic agent for glioblastoma, TMZ at different dosages as well as new therapeutic drugs targeting RNA modifying enzymes and compared to traditional 2D growth cell cultures.
Our results demonstrate that our co-culture model is optimal for evaluating the survival rate of the glioblastoma cells after being exposure to different therapeutic agents as well as for genetically dissect the invasive mechanisms of the different glioblastoma patient cells within the healthy brain organoid.
Overall, our 3D in vitro model of GBM provides an innovative approach to improve preclinical models of glioblastoma, giving in vitro human alternative platforms and thereby reducing the number of experimental animals.