AUTHOR=Silva Teresa P. , Bekman Evguenia P. , Fernandes Tiago G. , Vaz Sandra H. , Rodrigues Carlos A. V. , Diogo Maria Margarida , Cabral Joaquim M. S. , Carmo-Fonseca Maria 

TITLE=Maturation of Human Pluripotent Stem Cell-Derived Cerebellar Neurons in the Absence of Co-culture

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=Volume 8 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2020.00070

DOI=10.3389/fbioe.2020.00070

ISSN=2296-4185

ABSTRACT=The cerebellum plays a critical role in all vertebrates, and many neurological disorders are associated with cerebellum dysfunction. A major limitation in cerebellar research has been the lack of adequate disease models. As an alternative to animal models, cerebellar neurons have been differentiated from pluripotent stem cells. However, previous studies were able to produce only limited amounts of Purkinje cells. Moreover, in vitro generation of Purkinje cells so far required co-culture systems, which may introduce unknown components to the system. Here we describe a novel differentiation strategy that uses defined medium to generate Purkinje cells, granule cells, interneurons, and deep cerebellar nuclei projection neurons, that self-formed and matured into electrically active cells. Using a defined basal medium optimized for neuronal cell culture, we successfully promoted the maturation of cerebellar precursors without the need for co-culturing. We anticipate that our findings can be translated into better models for the study of cerebellar dysfunctions, and represent a valuable advance towards the development of autologous replacement strategies for treating cerebellar degenerative diseases.