title: Differentiation of neuroepithelial stem cells into functional dopaminergic neurons in 3D microfluidic cell culture.
abstract: A hallmark of Parkinson's disease is the progressive loss of nigrostriatal dopaminergic neurons. We derived human neuroepithelial cells from induced pluripotent stem cells and successfully differentiated them into dopaminergic neurons within phase-guided, three-dimensional microfluidic cell culture bioreactors. After 30 days of differentiation within the microfluidic bioreactors, in situ morphological, immunocytochemical and calcium imaging confirmed the presence of dopaminergic neurons that were spontaneously electrophysiologically active, a characteristic feature of nigrostriatal dopaminergic neurons in vivo. Differentiation was as efficient as in macroscopic culture, with up to 19% of differentiated neurons immunoreactive for tyrosine hydroxylase, the penultimate enzyme in the synthesis of dopamine. This new microfluidic cell culture model integrates the latest innovations in developmental biology and microfluidic cell culture to generate a biologically realistic and economically efficient route to personalised drug discovery for Parkinson's disease.
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7 avenue des Hauts-Fourneaux, L-4362 Esch-sur-Alzette, Luxembourg. ronan.mt.fleming@gmail.com.
authors.forename: Edinson Lucumi
authors.initials: EL
authors.lastname: Moreno
authors.forename: Siham
authors.initials: S
authors.lastname: Hachi
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hemmer
authors.forename: Sebastiaan J
authors.initials: SJ
authors.lastname: Trietsch
authors.forename: Aidos S
authors.initials: AS
authors.lastname: Baumuratov
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankemeier
authors.forename: Paul
authors.initials: P
authors.lastname: Vulto
authors.forename: Jens C
authors.initials: JC
authors.lastname: Schwamborn
authors.forename: Ronan M T
authors.initials: RM
authors.lastname: Fleming
mesh_terms: D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D059290:Dopaminergic Neurons / Q000166:cytology*; D004867:Equipment Design; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*