Improving and accelerating the differentiation and functional maturation of human stem cell-derived neurons: role of extracellular calcium and GABA.
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 GABAAreceptor 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.
School of Biosciences, Cardiff University, Cardiff, UK.
Paul J
PJ
Kemp
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
David J
DJ
Rushton
School of Biosciences, Cardiff University, Cardiff, UK.
Polina L
PL
Yarova
School of Biosciences, Cardiff University, Cardiff, UK.
Christian
C
Schnell
Department of Psychiatry and Human Behavior, University of California at Irvine, Irvine, CA, USA.
Charlene
C
Geater
Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Hatherly Laboratory, Exeter, EX4 4PS, UK.
Jane M
JM
Hancock
School of Biosciences, Cardiff University, Cardiff, UK.
Annalena
A
Wieland
School of Biosciences, Cardiff University, Cardiff, UK.
Alis
A
Hughes
School of Biosciences, Cardiff University, Cardiff, UK.
Luned
L
Badder
School of Biosciences, Cardiff University, Cardiff, UK.
Emma
E
Cope
School of Biosciences, Cardiff University, Cardiff, UK.
Daniela
D
Riccardi
Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Hatherly Laboratory, Exeter, EX4 4PS, UK.
Andrew D
AD
Randall
Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Hatherly Laboratory, Exeter, EX4 4PS, UK.
Jonathan T
JT
Brown
School of Biosciences, Cardiff University, Cardiff, UK.
Nicholas D
ND
Allen
School of Biosciences, Cardiff University, Cardiff, UK.
Vsevolod
V
Telezhkin
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D006801:Humans; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000378:metabolism* / Q000502:physiology*; D011963:Receptors, GABA-A / Q000378:metabolism*
D011963:Receptors, GABA-A; D002118:Calcium