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A cutting edge laboratory technique that turns human stem cells into brain-like tissues now recapitulates the development of the human brain more accurately than ever, according to a new study from the Case Western Reserve University School of Medicine . The study, published in Nature Methods shows how to grow brain "organoids" – self-organizing mini-spheres that now contain all the major types of cells found in the human cerebral cortex – in laboratory dishes. 19659002] Since its inception, so-called organoid technology has revolutionized the ability of researchers to generate and study human tissue in the laboratory. But when it comes to the brain, the models were not fully complete. This new study provides a missing link.
"We took the organoid system and added the third major cell type in the central nervous system – the oligodendrocytes – and now have a more accurate representation of the cellular interactions that occur during the human brain." Said Paul Tesar , Ph.D., Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics and Associate Professor of Genetics and Genome Sciences at Case Western Reserve University School of Medicine
Oligodendrocytes are essential for a brain in good They make myelin, a fatty substance that envelops and supports the connections of nerve cells, much like insulation around an electrical cord.Free myelin, the nerve cells can not communicate effectively and Many neurological diseases result from defects in myelin, including multiple sclerosis and rare pediatric genetic disorders.
"This is a powerful platform for understanding human development and neurological disease," said Tesar. "Thanks to stem cell technology, we can generate almost unlimited amounts of brain-like human tissue, creating a" mini-cortex "that contains neurons, astrocytes, and now oligodendrocytes that produce myelin.
Tesar and his colleagues have also demonstrated how their organo-enhanced system can be used to test myelin-enhancing drugs. "These organoids provide a way to predict the safety and efficacy of new myelin therapies on brain-like human tissue in the laboratory prior to clinical trials in humans," said Mayur Madhavan, PhD, co-first author of the study. The team treated organelles with previously identified drugs to improve myelin production in mice. For the first time, researchers used this model to test drugs that improve the production of human oligodendrocytes and myelin.
The research team also generated organelles in patients with Pelizaeus-Merzbacher disease. "Pelizaeus-Merzbacher's disease has been a complicated disorder to study because of the many mutations that can cause it and the inaccessibility of the patient's brain tissue," said Zachary Nevin, Ph.D., co-prime author of the study. allow us to directly study tissues similar to those of many patients simultaneously and test potential therapies. "The organoids generated by patients with three different Pelizaeus-Merzbacher disease mutations each had unique characteristics that could be targeted for drug treatment, and the results validate the structure as a versatile platform for observing and dissecting human myelin disease and testing individualized therapeutics.
"Our method allows the generation of human brain tissue in the laboratory of any patient," said Tesar. "More generally, he can accurately summarize how the human nervous system is constructed and identify what is wrong with certain neurological conditions. "
Robert H. Miller, PhD, and colleagues from George Washington joined the Tesar lab Valentina Fossati, Ph.D. , and colleagues at the New York Research Institute Stem Cell Foundation
This research was funded by grants from the National Institutes of Health, Pelizaeus-Merzbacher Disease Foundation, New York Stem Cell Foundation, Connor B. Judge Foundation, and the National Stem Cell Foundation. Philanthropic support was generously provided by the Peterson, Fakhouri, Long, Goodman, Geller, Galbut / Heil and Weidenthal families
