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Today, researchers at Stanford announced a new way of creating gobbets of human brain cells that look and act like real, living grey matter. The researchers took this striking result and named their product “human cortical spheroids,” or hCSs. In recent years, physiologists have learned to make and grow neural cells that look more and more like the real thing—most recently, by moving cell cultures beyond flat layers on the bottom of a Petri dish and into the third dimension. (Is this sounding like an ad for a 3-D movie?) A group out of Japan’s RIKEN Institute, led by the late Yoshiki Sasai, recently developed a cerebellum-like 3D culture. Jorgen Knoblich’s group at the Austrian Academy of Sciences created what they’re calling “cerebral organoids.” (Again, really: brain balls.) The spheroids made by Sergiu Paşca’s group at Stanford aren’t the first 3-D neural cultures, then. But they are the first that neuroscientists have been able to study functionally, looking at the electrical workings of their structure as a whole. Nobody understands the workings of the entire brain as it fires, but at least they can begin to figure out how these simplified 5-millimeter globes of cells work. To grow their spheroids, the group started with stem cells, cells (derived in this case from skin) that—with a little tweaking–grow into any kind of cell a researcher wants. It’s a property called “pluripotency.” But those cells won’t grow on their own; the team used a mixture of neuron-fertilizing molecules in a fluid bath. It worked. And the neurons didn’t just divide and grow: They actually echoed some of what would happen to cortical neurons in a real, live brain. The tiny, growing brain balls curled inward, developing multiple layers of neurons both deep and superficial, just like the human cortex does. Critically, after a certain amount of time the brain balls also started growing a type of cell called an astrocyte. These star-shaped cells provide physical and perhaps chemical support to neighboring neurons, so some of these brain balls stayed alive (and kept growing) much longer than they typically would—as old as 300 days. The cells also are critical for the formation of synapses, the junctions where neurons trade electrical messages. Because Paşca’s team was able to grow astrocytes alongside these cortical neurons, almost 90 percent of all the neurons inside the spheroids had active synapses, spontaneously sending electric missives to the network around them. They weren’t “thinking,” but they were doing something. The ultimate goal for these 3-D cultures is to mimic the brain’s actual cytoarchitecture as closely as possible. “The thing that everybody has been waiting for is ‘can we build a circuit in a dish?’” says Paşca. “We’re not there yet, but for now we have built a very complex neural network.”
‘Brain Balls’ Grown From Skin Cells Spark With Electricity | WIRED