Human cerebral organoids and neural 3D tissues in basic research, and their application to study neurological diseases

Written by Theresa S P Rothenbücher & Alberto Martinez-Serrano

Research with neural tissue in 3D is receiving great attention recently, since 3D offers a more physiological setting than traditional 2D cultures. In this commentary we overview and compare cerebral organoids and other 3D aggregated cell cultures. Last we briefly summarize examples of neurological diseases, mostly neurodevelopmental, where organoids are starting to be of help to understand the disease etiology, and in some cases to design therapies.
In vitro studies of neural tissue development, physiology, biochemistry, and molecular and cell biology are presently understood to be more relevant if experimental procedures are conducted in 3D as compared with 2D (monolayer cultures). The rationale behind this notion resides in the mutual interaction of cells in 3D, the possibility for the cells/tissue to generate its own extracellular matrix, and the cells’ capacity to establish 3D projections and multiple interactions, and that this would yield tissue constructs and organoids that better resemble the in vivo developmental processes, and the organization of functional, mature tissues, as well as the physiology and pathophysiology of neurodevelopmental processes, possibly including aging.

The 3D human neural tissue culture dates back to decades ago, early 1990s, when Weiss and collaborators described the generation of human neurospheres (spheroids), comprised of human neural stem cells, co-existing with differentiated cells [1]. The neurosphere culture method rapidly expanded and was extensively used, until presently. Interestingly, by that time and for many years, the focus was on how to proliferate the recently identified neural stem cells, rather than on the cytoarchitecture of the (putatively) self-organizing neural tissues in neurospheres. As a matter of interest, at that time the term ‘neural stem’ was not even widely accepted and therefore it was important to demonstrate their successful proliferation in culture. Consequently, neurosphere cultures were rendered as an experimental tool to proliferate the few neural stem cells that remained in such stem cell stage. Later on, the capacity to generate neurospheres, was used in clonogenic assays, to identify neural stem cells in a given neural cell preparation. But little, if any, attention was paid to the 3D organization of developing neural tissue in the 3D neurospheres.

Click here to read the full commentary in Future Neurology.

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