To model neurological diseases using brain organoids (BOs), there is a need for the development of terminally differentiated structures that reflect the structural and cellular complexity of mature brain tissue. Here we describe the developmental path of rat brain organoids (rBOs) into terminally differentiated brain structures. These organoids were compared to BOs derived from induced human pluripotent stem cells (iPSC) at the transcriptomic, proteomic and metabolomic level, showing that the rBOs present a higher degree of brain maturation. We further show that the rBOs can be used as an ex vivo avatar co-culture system to decipher important glioblastoma invasion parameters such as invasive cellular heterogeneity between patient-derived glioblastoma cells where key invasion parameters such as speed of single cell invasion and replacement of brain tissue by tumor cells can be measured and quantified in real-time. Finally, we show how this model can be used to assess therapeutic interventions, among others, directed toward neuro-gliomal α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor communication.
- Brain organoids