Document Detail


A new multistep induction protocol for the transdifferentiation of bone marrow stromal stem cells into GABAergic neuron-like cells.
MedLine Citation:
PMID:  23279829     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Bone marrow stromal stem cells (BMSC) are appropriate source of multipotent stem cells that are ideally suited for use in various cell-based therapies. It can be differentiated into neuronal-like cells under appropriate conditions. This study examined the effectiveness of co-stimulation of creatine and retinoic acid in increasing the differentiation of BMSC into GABAergic neuron-like cells (GNLC).
METHODS: BMSC isolated from the femurs and tibias of adult rats were cultured in DMEM/F12 medium supplemented with 10% FBS, pre-induced using β-mercaptoethanol β-ME) and induced using retinoic acid (RA) and creatine. Immunostaining of neurofilament 200 kDa, neurofilament 160 kDa, nestin, fibronectin, Gamma-amino butyric acid (GABA) and glutamic acid decarboxylase (GAD) 65/67 were used to evaluate the transdifferentiation of BMSC into GNLC and to evaluate the effectiveness of pre-induction and induction assays. The expression of genes that encode fibronectin, octamer-binding transcription factor 4 (Oct-4), GAD 65/67 and the vesicular GABA transporter was examined in BMSC and GNLC by using RT-PCR assays during transdifferentiation of BMSC into GLNC.
RESULTS: Co-stimulation with RA and creatine during the induction stage doubled the rates of GABAergic differentiation compared with induction using creatine alone, resulting in a 71.6% yield for GLNC. RT-PCR showed no expression of Oct-4 and fibronectin after the induction stage.
CONCLUSION: The results of this study showed that the application of β-ME, RA, and creatine induced the transdifferentiation of BMSC into GLNC.
Authors:
Shahram Darabi; Taki Tiraihi; AliReza Delshad; Majid Sadeghizadeh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Iranian biomedical journal     Volume:  17     ISSN:  2008-823X     ISO Abbreviation:  Iran. Biomed. J.     Publication Date:  2013  
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-06-25     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  9814853     Medline TA:  Iran Biomed J     Country:  Iran    
Other Details:
Languages:  eng     Pagination:  8-14     Citation Subset:  IM    
Affiliation:
Dept. of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Marrow Cells / cytology
Cell Transdifferentiation / drug effects*
Cells, Cultured
Creatine
Female
Fibronectins / biosynthesis
GABAergic Neurons / cytology,  metabolism*
Glutamate Decarboxylase / biosynthesis
Mercaptoethanol
Mesenchymal Stromal Cells / cytology,  metabolism*
Octamer Transcription Factor-3 / biosynthesis
Rats
Rats, Sprague-Dawley
Tretinoin
Vesicular Inhibitory Amino Acid Transport Proteins / biosynthesis
Chemical
Reg. No./Substance:
0/Fibronectins; 0/Octamer Transcription Factor-3; 0/Vesicular Inhibitory Amino Acid Transport Proteins; 0/vesicular GABA transporter; 302-79-4/Tretinoin; 57-00-1/Creatine; 60-24-2/Mercaptoethanol; EC 4.1.1.15/Glutamate Decarboxylase; EC 4.1.1.15/glutamate decarboxylase 2
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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