TMC PULSE

November 2019

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t m c » p u l s e | n o v e m b e r 2 0 1 9 t m c » p u l s e | n o v e m b e r 2 0 1 9 24 1709 Dryden Road, Houston, TX 77030 westinhoustonmedicalcenter.com After the 2017 publication of his technique in Stem Cell Reports, Krencik and his team released a fol- low-up paper in JoVE—the Journal of Visualized Experiments—that included a step-by-step video on how to engineer astrocytes into mini-brains. The 3D nature of the organ- oids provides significant benefits for research, and the accelerated maturation of Krencik's asteroids means more science can be done in less time. "By growing cells as large aggregates, as asteroids, you can study high density cells in complex three-dimensionality, similar to how they appear in the brain, and then, importantly, the cells form active connections to each other, otherwise known as neural networks," Krencik said. "Because you can grow them with intimate associations long-term, it allows them to form those connec- tions, and over time they can even display brainwave-like activity." The emittance of brainwaves from these organoids is an exciting step forward in the field. In August, researchers from the University of California in San Diego published a paper in Cell Stem Cell describing advanced electrical activity they observed in their brain organ- oids, which, notably, were created through their own unique method— not like Krencik's asteroids. "With the previous technology, we were seeing 3,000 spikes per minute, so neurons were firing at a rate of 3,000 in a minute, but we are actually detecting 300,000 spikes— so we are two orders of magnitude higher than we ever recorded in vitro, and that was shocking. We never expected to see that level of maturation—we never expected to see that from human neurons out- side the body," said Alysson Muotri, Ph.D., a biologist and professor at the University of California San Diego School of Medicine and a senior author of the paper. The brain oscillations followed a typical pattern of development of that of a growing fetus, Muotri added, with highly synchronized waves at approximately four months, but with increasingly complex oscillations by six to eight months. "The synchronization was just transient, and they become more complex, and that's what you would expect for the human brain," Muotri said. While Muotri stressed that their The large structure of the organoids allows us to study things that are important in neurosurgery, which you couldn't study with traditional cell culture systems. — ROBERT KRENCIK, PH.D. Neuroscientist at Houston Methodist Research Institute

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