(507b) Biomanufacturing of GBM Tumor Microenvironment Using a Small Scale Bioreactor

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor that originates from glioblastoma stem cells (GSCs). GSCs are able to create tumor microenvironment (TME) and reside in perivascular niche and hypoxic region where heterogeneity and cell to cell interaction exists. Many prior studies focused on modeling GBM using hydrogels, but these methods are limited to small scale with complex procedures and hardly represent complexity of GBM TME. Thus, there is a great need to develop a scalable platform for understanding of GBM TME and targeting GBM TME. Conventional organoid studies rely on growing them in serum-free media, resulting in sphere formation. This conventional method, however, often results in large random sphere aggregations and failing in controlling the size of the spheres. Here, we suggest a simple and more in vivo-like GBM culture method by optimizing the shear stress in a small scale bioreactor. We cultured patient-derived GBM cell lines with controlled size of GBM tumorsphere. GSCs grown under shear stress showed increase of Notch signals as well as pericytes markers which indicate characteristics of GSCs in perivascular niche. Further, GSCs grown under shear stress showed spatial increase of CD133 population. Collectively, GSC culture under optimized shear stress can model GSCs in perivascular niche including their microenvironment and GSCs expansion.