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Derivation of neural precursor cells from human ES cells at 3% O(2) is efficient, enhances survival and presents no barrier to regional specification and functional differentiation.

TitleDerivation of neural precursor cells from human ES cells at 3% O(2) is efficient, enhances survival and presents no barrier to regional specification and functional differentiation.
Publication TypeJournal Article
Year of Publication2011
AuthorsStacpoole SRL, Bilican B, Webber DJ, Luzhynskaya A, He XL, Compston A, Karadottir R, Franklin RJM, Chandran S
JournalCell Death Differ
Volume18
Issue6
Pagination1016-23
Date Published2011 Jun
ISSN1476-5403
KeywordsCell Death, Cell Differentiation, Cell Line, Embryonic Stem Cells, Humans, Mesencephalon, Models, Biological, Motor Neurons, Neural Stem Cells, Oxygen
Abstract

In vitro stem cell systems traditionally employ oxygen levels that are far removed from the in vivo situation. This study investigates whether an ambient environment containing a physiological oxygen level of 3% (normoxia) enables the generation of neural precursor cells (NPCs) from human embryonic stem cells (hESCs) and whether the resultant NPCs can undergo regional specification and functional maturation. We report robust and efficient neural conversion at 3% O(2), demonstration of tri-lineage potential of resultant NPCs and the subsequent electrophysiological maturation of neurons. We also show that NPCs derived under 3% O(2) can be differentiated long term in the absence of neurotrophins and can be readily specified into both spinal motor neurons and midbrain dopaminergic neurons. Finally, modelling the oxygen stress that occurs during transplantation, we demonstrate that in vitro transfer of NPCs from a 20 to 3% O(2) environment results in significant cell death, while maintenance in 3% O(2) is protective. Together these findings support 3% O(2) as a physiologically relevant system to study stem cell-derived neuronal differentiation and function as well as to model neuronal injury.

DOI10.1038/cdd.2010.171
Alternate JournalCell Death Differ.
PubMed ID21274009
PubMed Central IDPMC3091847
Grant ListG0300300 / / Medical Research Council / United Kingdom
G0701476 / / Medical Research Council / United Kingdom
G0800487 / / Medical Research Council / United Kingdom
G0800487(87418) / / Medical Research Council / United Kingdom
G0800784 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom