New study: lab-Petri-disk model not useful
It was hailed in a post I wrote, 8/9/2017, as the breakthrough for neuroscience research, growing mini human brains in lab-Petri-disk. However, a new study reports that the brain in a lab-petri dish model may not be as useful as I reported previously.
This study finding finds instead of differentiating normally into the brain’s distinctive cell type, cerebral organoids often express mixed genes typically found in different kinds of cells.
This study offers a more restrained perspective by showing that widely used organoid models fail to replicate even basic features of Brian’s development and organization, much less the complex circuity needed to model complex brain diseases or normal cognition.
Researches found that organdies do not develop the distinctive cell subtypes or regional circuit organizations that characterize typical human brain circuits. Since most human brain diseases are highly specific to particular cell types and circuits in the brain, this presents a grave challenge to efforts to use organdies to model these complex conditions accurately.
This study analysis revealed that instead of differentiating normally into the brain’s distinctive cell types, organoid cells appeared to experience an identity crisis: expressing a mixed bag of genes usually found in very different kinds of cells.
The brain’s ability to wire together different cell types into highly structured and regionally distinctive circuits are central not only to healthy brain function and cognition, but it is also these highly specific circuits that go awry in different ways in brain diseases such as autism, schizophrenia, and other psychiatric and neurological disorders.
These results suggest that neuroscientists’ ambitions to model complex brain organization in organoids will require a significant rethinking of how organoids are grown in the lab to try to reduce levels of cellular stress.
Acknowledgments & References
Arnold Kriegstein, MD, PhD, a professor of neurology in the UCSF Weill Institute for Neurosciences, John G. Bowes Distinguished Professor in Stem Cell and Tissue Biology, and director of the UCSF Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, Additional authors on the paper were Walter Mancia, Diane Jung, David Shin, Denise Allen, Dana Jung, Galina Schmunk, Alex Pollen, and Tomasz Nowakowski of UCSF; Maximilian Haeussler, of the UC Santa Cruz Genomics Institute; and Jahan Salma of the Center for Regenerative Medicine and Stem Cell Research at The Aga Khan University in Karachi, Pakistan.