Modl-41. Organotypic Brain Slice Culture Platform as a Novel Pre-Clinical Model for Patient Derived Cell Lines

Abstract

The lack of experimentally tractable models that recapitulate brain structure and function represents a major impediment in the development of novel treatment options for brain cancer. In vitro assays, though fast and high throughput, produce artificial results which do not fully encompass the clinically relevant outcome. Low passage patient derived cell lines offer an advantage over immortalized cell lines in terms of relation to the clinical presentation. Low passage patient derived cell lines, however, show slower growth and decreased tumorgenicity. We have previously shown that the use of organotypic brain slice culture (OBSCs) can recapitulate growth patterns and migration which is seen in vivo. We have further expanded the OBSCs to study their use as a model for patient derived cell lines. Some cell lines such as MS21, a human glioblastoma, or IFF109-DMG, a human pediatric diffuse midline glioma, are simply supported over a four-day time period, whereas other lines such as IFF105-DIPG, a pediatric human diffuse intrinsic pontine glioma, can grow over 3-fold in a 4-day time period. Additionally, we can assess treatment response to a variety of clinically relevant chemotherapeutics. The decreased variability with the OBSCs allows for the assessment of minute differences in treatment response. Overall, these results suggest the OBSC with patient derived cell lines have the potential to be effective models to accelerate preclinical evaluation of therapeutics and guide drug development towards more effective treatment strategies.