Posted on Jul 27, 2018, 12 a.m.
Missing cell type in brain organoids has been generated using a cutting edge laboratory technique to turn human stem cells into brain like tissue that recapitulates human brain development more accurately than ever according to researchers from Case Western Reserve University as published in Nature Methods.
The new study demonstrates how to grow brain organoids which are self organizing mini spheres that contain all major cell types found within the human cerebral cortex in laboratory dishes. Organoid technology has revolutionized ability to generate and study human tissue in a laboratory environment, but when it came to brain studies models were not complete until now with the missing link being provided.
The organoid system has had a third major cell type added into the central nervous system by the researchers called oligodendrocytes that provide a more accurate representation of cellular interaction occurring during human brain development. Oligodendrocytes are key to a healthy brain, making myelin that wraps and supports nerve cell connection, without myelin nerve cells can’t communicate effectively and deteriorate leading to neurological disease such as MS and rare pediatric genetic disorders.
Using stem cell technology a powerful platform has been created to understand human development and neurological disease generating nearly unlimited quantities of human brain like tissue in the lab. The new method creates a mini cortex containing astrocytes, neurons, and oligodendrocytes producing myelin.
The team demonstrated how their improved organoid system could be used to test myelin enhancing medications by treating organoids with drugs previously identified to enhance myelin production in model mice, for the first time using the model to test drugs that enhance generation of human oligodendrocytes and myelin.
Organoids were also generated from patients with Pelizaeus-Merzbacher disease which is a rare but fatal disorder that has been difficult to study due to many mutations that can cause it and the inaccessibility of patient brain tissue. These new organoids generated from patients with 3 different disease mutations each demonstrated unique characteristics that could be targeted for drug treatments. These additional findings even further validate the setup as a versatile platform to observe and dissect human myelin disease and test individualized therapeutics, and more broadly it can recapitulate how the human nervous system is built and help to identify what goes wrong in certain neurological conditions.
Materials provided by Case Western Reserve University.
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Mayur Madhavan, Zachary S. Nevin, H. Elizabeth Shick, Eric Garrison, Cheryl Clarkson-Paredes, Molly Karl, Benjamin L. L. Clayton, Daniel C. Factor, Kevin C. Allan, Lilianne Barbar, Tanya Jain, Panagiotis Douvaras, Valentina Fossati, Robert H. Miller, Paul J. Tesar. Induction of myelinating oligodendrocytes in human cortical spheroids. Nature Methods, 2018; DOI: 10.1038/s41592-018-0081-4