Accelerated neuronal differentiation toward motor neuron lineage from human embryonic stem cell line (H9)

David Lu, Eric Y T Chen, Philip Lee, Yung Chen Wang, Wendy Ching, Christopher Markey, Chase Gulstrom, Li Ching Chen, Thien Nguyen, Wei Chun Chin

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Motor neurons loss plays a pivotal role in the pathoetiology of various debilitating diseases such as, but not limited to, amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy, progressive bulbar palsy, pseudobulbar palsy, and spinal muscular atrophy. However, advancement in motor neuron replacement therapy has been significantly constrained by the difficulties in large-scale production at a cost-effective manner. Current methods to derive motor neuron heavily rely on biochemical stimulation, chemical biological screening, and complex physical cues. These existing methods are seriously challenged by extensive time requirements and poor yields. An innovative approach that overcomes prior hurdles and enhances the rate of successful motor neuron transplantation in patients is of critical demand. Iron, a trace element, is indispensable for the normal development and function of the central nervous system. Whether ferric ions promote neuronal differentiation and subsequently promote motor neuron lineage has never been considered. Here, we demonstrate that elevated iron concentration can drastically accelerate the differentiation of human embryonic stem cells (hESCs) toward motor neuron lineage potentially via a transferrin mediated pathway. HB9 expression in 500 nM iron-treated hESCs is approximately twofold higher than the control. Moreover, iron treatment generated more matured and functional motor neuron-like cells that are ∼1.5 times more sensitive to depolarization when compared to the control. Our methodology renders an expedited approach to harvest motor neuron-like cells for disease, traumatic injury regeneration, and drug screening.

Original languageEnglish
Pages (from-to)242-252
Number of pages11
JournalTissue Engineering - Part C: Methods
Volume21
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

Fingerprint

Motor Neurons
Stem cells
Neurons
Cell Line
Iron
Spinal Muscular Atrophy
Screening
Pseudobulbar Palsy
Progressive Bulbar Palsy
Chemical Stimulation
Motor Neuron Disease
Preclinical Drug Evaluations
Human Embryonic Stem Cells
Depolarization
Amyotrophic Lateral Sclerosis
Trace Elements
Neurology
Transferrin
Trace elements
Cues

ASJC Scopus subject areas

  • Biomedical Engineering
  • Bioengineering
  • Medicine (miscellaneous)

Cite this

Accelerated neuronal differentiation toward motor neuron lineage from human embryonic stem cell line (H9). / Lu, David; Chen, Eric Y T; Lee, Philip; Wang, Yung Chen; Ching, Wendy; Markey, Christopher; Gulstrom, Chase; Chen, Li Ching; Nguyen, Thien; Chin, Wei Chun.

In: Tissue Engineering - Part C: Methods, Vol. 21, No. 3, 01.03.2015, p. 242-252.

Research output: Contribution to journalArticle

Lu, D, Chen, EYT, Lee, P, Wang, YC, Ching, W, Markey, C, Gulstrom, C, Chen, LC, Nguyen, T & Chin, WC 2015, 'Accelerated neuronal differentiation toward motor neuron lineage from human embryonic stem cell line (H9)', Tissue Engineering - Part C: Methods, vol. 21, no. 3, pp. 242-252. https://doi.org/10.1089/ten.tec.2013.0725
Lu, David ; Chen, Eric Y T ; Lee, Philip ; Wang, Yung Chen ; Ching, Wendy ; Markey, Christopher ; Gulstrom, Chase ; Chen, Li Ching ; Nguyen, Thien ; Chin, Wei Chun. / Accelerated neuronal differentiation toward motor neuron lineage from human embryonic stem cell line (H9). In: Tissue Engineering - Part C: Methods. 2015 ; Vol. 21, No. 3. pp. 242-252.
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