3D Cortical Microtissues

The development of 3D brain cultures has had a transformative impact on the field of predictive biology and is the foundation for much of the research at the Hoffman-Kim Lab. Using rodent cortical cells or human stem cells, researchers can create ‘mini-brains’ in a high-throughput manner. These mini-brains accurately represent features of in vivo neuronal tissue, while allowing us to maintain control over the system’s environment. They contain a diversity of cell types, including neurons, astrocytes, microglia, oligodendrocytes, neural precursor cells. Further, they display brain-like electrical activity and stiffness as well as capillary-like networks.

These features – reproducibility, control, and comparatively high fidelity – make 3D culture systems a very attractive target for drug development, toxicity screening, and in vitro disease and injury modeling. Our work aims to use cortical microtissues to model pathophysiology of various disease states, including traumatic brain injury, ischemic injury, and glioblastoma. The goal of these studies is to offer new avenues of investigation into complex neurological phenomena.

To derive cortical spheroids, primary rat cortices are extracted and dissociated into a single cell suspension. They are then seeded into 96 well agarose gels where they spontaneously self-assemble into cortical spheroids containing diverse cell types.

The image above depicts a cortical spheroid after 14 days of culture viewed through a confocal microscope. The image shows cell nuclei (blue), astrocytes (green), microglia (pink), and neuronal structures (red).