Scientists Develop New Protocol for Generating Brain Organoids
In a collaborative study between Case Western Reserve University, the New York Stem Cell Foundation (NYSCF) Research Institute, and George Washington University, researchers have developed a new procedure for generating miniature 3D tissue called “brain organoids” from human stem cells. These organoids contain all major cell types in the cerebral cortex, modeling the brain’s structure and function more closely than ever.
The new protocol, published in Nature Methods, is important because it adds a key ingredient that past organoids were missing: oligodendrocytes. Oligodendrocytes are brain cells that produce myelin, a substance that coats nerve fibers and helps neurons send signals. Oligodendrocytes are important for typical brain function and are suspected to play a role in diseases that result in a loss of myelin, such as multiple sclerosis.
In the study, the researchers exposed their organoids to a set of specific growth factors that allowed for the formation of oligodendrocyte progenitors, which then differentiated into oligodendrocytes and kicked off the myelination process.
The team then then tested the model’s ability to recapitulate the pathology of a myelin disorder by generating organoids from the cells of patients with Pelizaeus–Merzbacher disease—a rare but fatal genetic disorder. Researchers found that the organoids successfully modeled the characteristics of the disease, and organoids generated from patients with different mutations showed unique characteristics that could serve as potential targets for therapeutic intervention.
Finally, NYSCF researchers replicated the protocol independently using a different embryonic stem cell line, which was critical to demonstrate reproducibility.
The study was led by Paul Tesar, DPhil, the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics and associate professor of genetics and genome sciences at Case Western Reserve University Medical School. Dr. Tesar also received a NYSCF – Robertson Stem Cell Investigator Award in 2010 and was a recipient of the NYSCF – Robertson Stem Cell Prize in 2017. He and Dr. Valentina Fossati, PhD, NYSCF Senior Principal Investigator, have been longtime collaborators who next plan to use the new protocol to test the effectiveness of novel multiple sclerosis drugs.
“NYSCF is committed to developing and disseminating robust protocols that accelerate stem cell and neuroscience research,” says Susan L. Solomon, NYSCF CEO. “The protocol outlined in this study will let researchers ask more advanced questions and gain more accurate knowledge about the complexities of neurodegenerative diseases, which will inform the development of better treatments down the road.”
Read the press release here.