title: Healthy human CSF promotes glial differentiation of hESC-derived neural cells while retaining spontaneous activity in existing neuronal networks.
abstract: The possibilities of human pluripotent stem cell-derived neural cells from the basic research tool to a treatment option in regenerative medicine have been well recognized. These cells also offer an interesting tool for in vitro models of neuronal networks to be used for drug screening and neurotoxicological studies and for patient/disease specific in vitro models. Here, as aiming to develop a reductionistic in vitro human neuronal network model, we tested whether human embryonic stem cell (hESC)-derived neural cells could be cultured in human cerebrospinal fluid (CSF) in order to better mimic the in vivo conditions. Our results showed that CSF altered the differentiation of hESC-derived neural cells towards glial cells at the expense of neuronal differentiation. The proliferation rate was reduced in CSF cultures. However, even though the use of CSF as the culture medium altered the glial vs. neuronal differentiation rate, the pre-existing spontaneous activity of the neuronal networks persisted throughout the study. These results suggest that it is possible to develop fully human cell and culture-based environments that can further be modified for various in vitro modeling purposes.
authors.affiliation: Critical Care Medicine Research Group, Department of Intensive Care Unit, Tampere University Hospital , FI-33521 Tampere , Finland ; NeuroGroup, Institute of Biomedical Technology/BioMediTech, University of Tampere , FI-33520 Tampere , Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Kiiski
authors.forename: Riikka
authors.initials: R
authors.lastname: Aänismaa
authors.forename: Jyrki
authors.initials: J
authors.lastname: Tenhunen
authors.forename: Sanna
authors.initials: S
authors.lastname: Hagman
authors.forename: Laura
authors.initials: L
authors.lastname: Ylä-Outinen
authors.forename: Antti
authors.initials: A
authors.lastname: Aho
authors.forename: Arvi
authors.initials: A
authors.lastname: Yli-Hankala
authors.forename: Stepani
authors.initials: S
authors.lastname: Bendel
authors.forename: Heli
authors.initials: H
authors.lastname: Skottman
authors.forename: Susanna
authors.initials: S
authors.lastname: Narkilahti
keywords: Astrocyte; Microelectrode array; Network activity; Neuron; Oligodendrocyte; Stem cell