The cerebral organoid has been described as the size of a pea, but please don’t eat it. It is not a food. It is not something floating around in space either. Ladies and gentlemen, allow me to introduce the first ever man-made tissue that actually forms discrete areas of the human brain, and works like one too–well, except for the “thinking” part. I read about the cerebral organoid in a paper published August 28 in the journal, Nature. Electronic sounds from the new Daft Punk album, Random Access Memories, teleported me into a world that seemed like science fiction as a team of Austrian and British scientists described an unknown mystery. Their story was the most futuristic tale I had heard since Clarity and the invisible brain. This was big news, like landing on a moon made of…brain. So, what happens when you take some skin cells, mix them with some protein and then drop those into what’s called a spinning bioreactor? You grow a brain. And that’s exactly what they did in this study, twice. They started with a tiny one, and then made an even tinier one to model that of a patient suffering from primary microcephaly. Although it would have been cool to transplant the mini-brain into the skull of a pygmy marmoset, it would not have been ethical or rational, so they settled on looking at brain development.
In primary microcephaly, a genetic mutation causes a person to grow a brain much smaller than average. Patients often suffer cognitive impairments and live shorter lives. One mutation relates to a protein called CDK5RAP2. Although it’s well known, scientists failed to mimic the decreased brain size in a mouse model where they manipulated the protein.
They went to work with epithelial stem cells from a microcephalic patient and a healthy one. Other scientists have grown brain tissue like this before, but these guys embedded the cells in a protein matrix and 3-D culture to allow for a structure not possible in a Petri dish and then threw it into a spinning bioreactor to enhance nutrient absorption.
The cells, loving their new environment, grew rapidly into brain tissue. Neural identity emerged in eight to ten days, and defined brain regions formed in about a month. Maintained in the bioreactor, what scientists termed cerebral organoids, could survive up to ten months. The organoids recapitulated areas of the developing brain called progenitor zones which are filled with radial glial cells. Progenitor cells are just mature cortical neuron subtypes. These things make the human brain unique from other mammals. Later, the team used typical experiments that elicit and inhibit neural firing to check out how the mature organoid worked, and guess what? They behaved like neurons in the brain. As for the patient-derived cerebral organoid, it was, indeed, much smaller. In this “brain,” the tissue developed into distinct brain areas earlier and had fewer progenitor cells.
Their work tells us that hope for understanding developmental diseases rests easy in the cerebral organoid. Apologies to all you Sci-Fi nerds–there won’t be a brain transplant anytime soon. The human brain is just too complex, and the cerebral organoid is too tiny (it’d just bounce around in there). -by JoAnna Klein
