Abstract There is an urgent need for new therapeutics for pediatric gliomas, but current in vitro and patient derived xenograft (PDX) models lose heterogeneity and fidelity to the patient’s original tumor as they are expanded to generate material for screening assays. Further, since pediatric gliomas are driven, at least in part, by transcriptional dysregulation as opposed to the high number of somatic mutations commonly driving adult cancers, prolonged culture in non-native growth environments is particularly problematic. 3-D stem cell derived tissue cultures such as organoids more accurately mimic in vivo tissue architecture providing a tumor microenvironment with the potential to preserve the transcriptomic state of pediatric glioma cells grown in vitro. To test this, we established conditions that enable low passage pediatric glioma cell lines to invade into cerebral organoids and measured how their gene expression changes via RNA sequencing. These results were compared to RNA sequencing done on the parental tumor. Preliminary results show substantial rescue of tumor transcriptomic state by coculturing the cell lines with organoids. This showcases how stem cell based organoids can be used to expand patient derived tissues in an environment more faithful to the primary tumor. Additionally, this system is more amenable to high throughput assays than PDX models. By establishing the relevance of this preclinical culturing platform it can one day be used to expand patient derived tissues in a more biologically accurate way and allow for more rapid, accurate cancer therapeutic screening.
Brail et al. (Fri,) studied this question.