Orthotopic Transplantation of Human Paediatric High-Grade Glioma in Zebrafish Larvae

Brain tumours are the most common cause of death among children with solid tumours, and high-grade gliomas (HGG) are among the most devastating forms with very poor outcomes. In the search for more effective treatments for paediatric HGG, there is a need for better experimental models. To date, there are no xenograft zebrafish models developed for human paediatric HGG; existing models rely on adult cells. The use of paediatric models is of great importance since it is well known that the genetic and epigenetic mechanisms behind adult and paediatric disease differ greatly. In this study, we present a clinically relevant in vivo model based on paediatric primary glioma stem cell (GSC) cultures, which after orthotopic injection into the zebrafish larvae, can be monitored using confocal imaging over time. We show that cells invade the brain tissue and can be followed up to 8 days post-injection while they establish in the fore/mid brain. This model offers an in vivo system where tumour invasion can be monitored and drug treatments quickly be evaluated. The possibility to monitor patient-specific cells has the potential to contribute to a better understanding of cellular behaviour and personalised treatments in the future.

Automated summary

Brain tumours are a leading cause of death in children with solid tumours, and high-grade gliomas are particularly devastating. This study presents a clinically relevant in vivo model for paediatric glioma using zebrafish larvae and primary glioma stem cell cultures. The model allows for the monitoring of tumour invasion and evaluation of drug treatments. This research has the potential to improve understanding of cellular behaviour and personalized treatments for paediatric high-grade gliomas.