Neural Progenitor Cells Derived from Human Embryonic Stem Cells as an Origin of Dopaminergic Neurons
Author(s)
Noisa, P
Raivio, T
Cui, W
Type
Journal Article
Abstract
Human embryonic stem cells (hESCs) are able to proliferate in vitro indefinitely without losing their ability to differentiate into multiple cell types upon exposure to appropriate signals. Particularly, the ability of hESCs to differentiate into neuronal subtypes is fundamental to develop cell-based therapies for several neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. In this study, we differentiated hESCs to dopaminergic neurons via an intermediate stage, neural progenitor cells (NPCs). hESCs were induced to neural progenitor cells by Dorsomorphin, a small molecule that inhibits BMP signalling. The resulting neural progenitor cells exhibited neural bipolarity with high expression of neural progenitor genes and possessed multipotential differentiation ability. CBF1 and bFGF responsiveness of these hES-NP cells suggested their similarity to embryonic neural progenitor cells. A substantial number of dopaminergic neurons were derived from hES-NP cells upon supplementation of FGF8 and SHH, key dopaminergic neuron inducers. Importantly, multiple markers of midbrain neurons were detected, including NURR1, PITX3, and EN1, suggesting that hESC-derived dopaminergic neurons attained the midbrain identity. Altogether, this work underscored the generation of neural progenitor cells that retain the properties of embryonic neural progenitor cells. These cells will serve as an unlimited source for the derivation of dopaminergic neurons, which might be applicable for treating patients with Parkinson’s disease.
Date Issued
2015-04-14
Date Acceptance
2015-04-14
Citation
Stem Cells International, 2015, 2015
ISSN
1687-9678
Publisher
Hindawi Publishing Corporation
Journal / Book Title
Stem Cells International
Volume
2015
Copyright Statement
© 2015 Parinya Noisa et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell & Tissue Engineering
Cell Biology
EFFICIENT DIFFERENTIATION
SONIC HEDGEHOG
IPS CELLS
HUMAN ES
IN-VIVO
MIDBRAIN
NOTCH
ACTIVATION
GENERATION
INDUCTION
Publication Status
Published
Article Number
647437