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Improving and accelerating the differentiation and functional maturation of human stem cell‐derived neurons: role of extracellular calcium and GABA
Author(s) -
Kemp Paul J.,
Rushton David J.,
Yarova Polina L.,
Schnell Christian,
Geater Charlene,
Hancock Jane M.,
Wieland Annalena,
Hughes Alis,
Badder Luned,
Cope Emma,
Riccardi Daniela,
Randall Andrew D.,
Brown Jonathan T.,
Allen Nicholas D.,
Telezhkin Vsevolod
Publication year - 2016
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp270655
Subject(s) - induced pluripotent stem cell , neurogenesis , neuroscience , biology , stem cell , embryonic stem cell , progenitor cell , neural stem cell , calcium imaging , microbiology and biotechnology , calcium , medicine , genetics , gene
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 GABA A 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.