It’s difficult to control the growth of whole brain organoids, says Ming in an interview with The Scientist, and researchers end up with structures that are highly variable and contain a randomly distributed mish-mash of brain regions. Instead, Ming and her team were able to grow forebrains using custom-made bioreactors and a cocktail of specialized growth signals.
The researchers’ forebrain organoids simulate human cortical development “from conception to the first trimester,” says Ming, and harbor other human-specific traits—including a cortex composed of distinct layers as well as the presence of radial glial cells within a region resembling the evolutionarily recent outer subventricular zone.
When the team exposed these more-sophisticated structures to Zika, the virus preferred to infect neural stem cells over mature neurons, confirming earlier results.
Ming and her team also selectively infected their forebrain organoids with ZIKA-NS2A, one of Zika’s seven non-structural proteins, demonstrating that this specific protein alone can disrupt the growth of radial glial cells.
The researchers cultivated these forebrain-specific organoids using 3-D printed, miniaturized bioreactors, designed with the help of three high school interns. The bioreactors consisted of small containers filled with culture media that were motorized to spin, preventing the growing cells from sticking to the walls of the container and thereby increasing the diffusion of nutrients and oxygen.
An added bonus is that the team’s custom contraptions require less culture media, which is expensive; the larger containers that come with typical bioreactors require it in hefty amounts.
Ming and her team have also designed protocols for growing other regions of the brain, including the hypothalamus and mid-brain structures.