Establishment of a glioblastoma in vitro (in)complete resection dual co-culture model suitable for drug testing

Abstract

BackgroundThe treatment of glioblastomas (GBM) is still a clinical challenge. Current GBM therapeutic plans focus on the development of new strategies for local drug administration in the tumor cavity to realize an efficient long-term treatment with small side-effects. Here, different amounts of residual GBM cells and healthy brain cells define the microenvironment of the tumor cavity after individual surgical GBM resection (complete or incomplete). MethodsWe evaluated available in vivo data and determined the required amounts and numerical ratios of GBM and healthy brain cells for our in vitro (in)complete resection dual co-culture model. We applied a generic two-drug treatment [Temozolomide (TMZ) in combination with AT101, followed by single AT101 treatment] strategy and analyzed the results in comparison with appropriate mono-culture systems to prove the applicability of our model. ResultsWe established a suitable GBM dual co-culture model, mimicking the complete and incomplete resection in vitro, giving stable and reliable results on drug testing. Both dual co-culture conditions protectively influenced on cell death and growth rates of primary GBMs when treated with TMZ+AT101/AT101, although the treatment strategy per se was still efficient. Cell death of astrocytes correlated with amounts of increasing GBM cell numbers in the incomplete resection model upon drug treatment, and probably GBM-released chemokine and cytokines were involved in this interplay. ConclusionsOur results suggest that this dual co-culture model provides a biologically relevant platform for the discovery and compound screening of local GBM treatment strategies.