Document Detail


All-trans-retinoid acid induces the differentiation of encapsulated mouse embryonic stem cells into GABAergic neurons.
MedLine Citation:
PMID:  22466603     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Embryonic stem (ES) cells are pluripotent cells that can differentiate into all three main germ layers: endoderm, mesoderm, and ectoderm. Although a number of methods have been developed to differentiate ES cells into neuronal phenotypes such as sensory and motor neurons, the efficient generation of GABAergic interneurons from ES cells still presents an ongoing challenge. Because the main output of inhibitory GABAergic interneurons is the gamma-aminobutyric-acid (GABA), a neurotransmitter whose controlled homeostasis is required for normal brain function, the efficient generation in culture of functional interneurons may have future implications on the treatment of neurological disorders such as epilepsy, autism, and schizophrenia. The goal of this work was to examine the generation of GABAergic neurons from mouse ES cells by comparing an embryoid body-based methodology versus a hydrogel-based encapsulation protocol that involves the use of all-trans-retinoid acid (RA). We observed that (1) there was a 2-fold increase in neuronal differentiation in encapsulated versus non-encapsulated cells and (2) there was an increase in the specificity for interneuronal differentiation in encapsulated cells, as assessed by mRNA expression and electrophysiology approaches. Furthermore, our results indicate that most of the neurons obtained from encapsulated mouse ES cells are GABA-positive (∼87%). Thus, these results suggest that combining encapsulation of ES cells and RA treatment provide a more efficient and scalable differentiation strategy for the generation in culture of functional GABAergic interneurons. This technology may have implications for future cell replacement therapies and the treatment of CNS disorders.
Authors:
Cynthia Addae; Xiaoping Yi; Ramkishore Gernapudi; Henrique Cheng; Alberto Musto; Eduardo Martinez-Ceballos
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-03-30
Journal Detail:
Title:  Differentiation; research in biological diversity     Volume:  83     ISSN:  1432-0436     ISO Abbreviation:  Differentiation     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-04-23     Completed Date:  2012-09-25     Revised Date:  2014-04-18    
Medline Journal Info:
Nlm Unique ID:  0401650     Medline TA:  Differentiation     Country:  England    
Other Details:
Languages:  eng     Pagination:  233-41     Citation Subset:  IM    
Copyright Information:
Published by Elsevier B.V.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / growth & development,  metabolism
Cell Differentiation* / drug effects
Cell Line
Cell- and Tissue-Based Therapy*
Embryoid Bodies / cytology,  metabolism
Embryonic Stem Cells / cytology*,  transplantation
GABAergic Neurons / cytology*,  metabolism
Gene Expression Regulation, Developmental / drug effects
Hydrogel / chemistry
Leukemia Inhibitory Factor / metabolism
Mice
Potassium Channels / metabolism
Tretinoin / pharmacology*
gamma-Aminobutyric Acid / metabolism
Grant Support
ID/Acronym/Agency:
5P20RR016456-11/RR/NCRR NIH HHS; 8P20GM103424-11/GM/NIGMS NIH HHS; P20 GM103424/GM/NIGMS NIH HHS; P20 GM103424-11/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Leukemia Inhibitory Factor; 0/Potassium Channels; 25852-47-5/Hydrogel; 56-12-2/gamma-Aminobutyric Acid; 5688UTC01R/Tretinoin
Comments/Corrections

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