Analysis of the potential role of photocurable hydrogel in patient-derived glioblastoma organoid culture through RNA sequencing

Abstract

Patient-derived glioblastoma organoid (GBO) growth in hydrogels recapitulates key features of parental tumors, making GBOs a useful tool for fundamental research on cancer biology and offer deeper insight into the development of innovative therapeutic strategies for cancer treatment. Matrigel as a natural hydrogel has been widely used for 3D culture in most tumor organoid studies, but the volatility in its biochemical and biophysical properties makes it difficult to be further applied in GBO cultures. Thus, several kinds of biomimetic hydrogels from synthetic or biological polymers have been developed for tumor organoid growth. Here, we innovatively utilize a photocurable hydrogel-based biomimetic instructive system containing gelatin methacryloyl (GelMA) mixed with a hyaluronic acid (HA) hydrogel as a scaffold for generating GBOs. Furthermore, we evaluated the GBO biological properties at the transcriptome level, which showed that GBOs cultured with this hydrogel retain the expression profile of key neurodevelopmental markers, driving mutations and alternative splicing of parental tumors. Notably, GBOs cultured with the photocurable hydrogel may provide a platform for precision cancer medicine, bridging the gap between basic research and clinical application. Although significant challenges remain, biomimetic hydrogels can provide an exceptional window for the construction of tumor organoids to ensure the accuracy of the research and clinical data.