Improving And Accelerating The Differentiation And Functional Maturation Of Human Stem Cell-Derived Neurons: Role Of Extracellular Calcium And Gaba
JOURNAL OF PHYSIOLOGY-LONDON(2016)
摘要
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 nhibitory 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 neuro-degenerative and neuropsychiatric disorders, such as Huntington's disease, Parkinson's disease, Alzheimer's disease and Schizophrenia.
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