Mini Brain Organoids Upshift The Understanding Of Brain Diseases

Three-dimensional human stem cell-derived 'Mini Brain' organoids can mature in a manner that is strikingly similar to human brain development, following an internal clock that guides their maturation in synchrony with the timeline of human brain development, as per a study at UCLA and Stanford University, published in the journal Nature Neuroscience Organoids are small, self-organized 3D tissue cultures that are derived from stem cells. They are capable of being crafted to replicate much of the complexity of an organ or to express selected aspects of it like producing only certain types of cells.

Human brain organoids are created using induced pluripotent stem cells, also known as iPS cells, which are derived from skin or blood cells. These cells are reprogrammed back to an embryonic stem cell-like state that allows the scientists to create any cell type.

These iPS cells are then presented to a specific blend of chemicals that influences them to create the cell of a certain region of the brain. With time and the appropriate conditions, the cells self-organize to create 3D structures that faithfully replicate several aspects of human brain development.

The Mini Brain Organoids

Human brain organoids have been under developmental research for many years to study neurological and neurodevelopmental disorders like autism, epilepsy, and schizophrenia. Human stem cell-derived organoids can alter the act of medication by providing researchers unprecedented insights into how complex organs including the brain develop and respond to disease.

"There is huge interest in stem cell models of human disease. This work represents an important milestone by showing which aspects of human brain development are modeled with the highest fidelity and which specific genes are behaving well in vitro and when best to model them. Equally important, we provide a framework based on unbiased genomic analyses for assessing how well in vitro models model in vivo development and function", says Geschwind, MD, Ph.D., MacDonald Distinguished Professor in Human Genetics at the David Geffen School of Medicine at UCLA, member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, and the senior associate dean and associate vice chancellor and director of the Institute for Precision Health at UCLA.

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The far-reaching conviction that the cells that make up these organoids remain stuck in a developmental state analogous to the cells seen in fetal development has greatly obstructed the utility of these models. However, the present study demonstrates the possibility to grow the cells to maturity would thereby allow in better understanding of adult-onset diseases such as dementia or schizophrenia.

"We show that these 3D brain organoids follow an internal clock, which progresses in a laboratory environment in parallel to what occurs inside a living organism. This is a remarkable finding -- we show that they reach post-natal maturity around 280 days in culture, and after that begin to model aspects of the infant brain, including known physiological changes in neurotransmitter signaling", says the first author Aaron Gordon, Ph.D., a postdoc in The Geschwind Lab at the David Geffen School of Medicine at UCLA.

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Source-Medindia