Improving and accelerating the differentiation and functional maturation of human stem cell-derived neurons: role of extracellular calcium and GABA

Kemp, Paul J ORCID: https://orcid.org/0000-0003-2773-973X, Rushton, David J., Yarova, Polina, Schnell, Christian, Geater, Charlene, Hancock, Jane M., Wieland, Annalena, Hughes, Alis, Badder, Luned, Cope, Emma Louise, Riccardi, Daniela ORCID: https://orcid.org/0000-0002-7322-3163, Randall, Andrew, Brown, Jonathan T., Allen, Nicholas Denby ORCID: https://orcid.org/0000-0003-4009-186X and Telezhkin, Vsevolod ORCID: https://orcid.org/0000-0002-5054-8774 2016. Improving and accelerating the differentiation and functional maturation of human stem cell-derived neurons: role of extracellular calcium and GABA. The Journal of Physiology 594 (22) , pp. 6583-6594. 10.1113/JP270655

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Abstract

Neurons differentiated from pluripotent stem cells using established neural culture conditions often exhibit functional deficits. Recently, we have developed enhanced media which both synchronize the neurogenesis of pluripotent stem cell-derived neural progenitors and accelerate their functional maturation; together these media are termed SynaptoJuice. This pair of media are pro-synaptogenic and generate authentic, mature synaptic networks of connected forebrain neurons from a variety of induced pluripotent and embryonic stem cell lines. Such enhanced rate and extent of synchronized maturation of pluripotent stem cell-derived neural progenitor cells generates neurons which are characterized by a relatively hyperpolarized resting membrane potential, higher spontaneous and induced action potential activity, enhanced synaptic activity, more complete development of a mature inhibitory GABAA receptor phenotype and faster production of electrical network activity when compared to standard differentiation media. This entire process – from pre-patterned neural progenitor to active neuron – takes 3 weeks or less, making it an ideal platform for drug discovery and disease modelling in the fields of human neurodegenerative and neuropsychiatric disorders, such as Huntington's disease, Parkinson's disease, Alzheimer's disease and Schizophrenia.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
Publisher:	The Physiological Society
ISSN:	0022-3751
Date of First Compliant Deposit:	15 November 2016
Date of Acceptance:	24 August 2016
Last Modified:	07 Nov 2024 20:46
URI:	https://orca.cardiff.ac.uk/id/eprint/96146

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