Document Detail


Astrocytes derived from fetal neural progenitor cells as a novel source for therapeutic adenosine delivery.
MedLine Citation:
PMID:  20688264     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Intracerebral delivery of anti-epileptic compounds represents a novel strategy for the treatment of refractory epilepsy. Adenosine is a possible candidate for local delivery based on its proven anti-epileptic effects. Neural stem cells constitute an ideal cell source for intracerebral transplantation and long-term drug delivery. In order to develop a cell-based system for the long-term delivery of adenosine, we isolated neural progenitor cells from adenosine kinase deficient mice (Adk(-/-)) and compared their differentiation potential and adenosine release properties with corresponding wild-type cells.
METHODS: Fetal neural progenitor cells were isolated from the brains of Adk(-/-) and C57BL/6 mice fetuses and expanded in vitro. Before and after neural differentiation, supernatants were collected and assayed for adenosine release using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
RESULTS: Adk(-/-) cells secreted significantly more adenosine compared to wild-type cells at any time point of differentiation. Undifferentiated Adk(-/-) cells secreted 137+/-5 ng adenosine per 10(5) cells during 24 h in culture, compared to 11+/-1 ng released from corresponding wild-type cells. Adenosine release was maintained after differentiation as differentiated Adk(-/-) cells continued to release significantly more adenosine per 24 h (47+/-1 ng per 10(5) cells) compared to wild-type cells (3+/-0.2 ng per 10(5) cells).
CONCLUSIONS: Fetal neural progenitor cells isolated from Adk(-/-) mice--but not those from C57BL/6 mice--release amounts of adenosine considered to be of therapeutic relevance.
Authors:
Annelies Van Dycke; Robrecht Raedt; Alain Verstraete; Panos Theofilas; Wytse Wadman; Kristl Vonck; Detlev Boison; Paul Boon
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-06-17
Journal Detail:
Title:  Seizure : the journal of the British Epilepsy Association     Volume:  19     ISSN:  1532-2688     ISO Abbreviation:  Seizure     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-06     Completed Date:  2010-12-02     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9306979     Medline TA:  Seizure     Country:  England    
Other Details:
Languages:  eng     Pagination:  390-6     Citation Subset:  IM    
Copyright Information:
2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Affiliation:
Laboratory for Clinical and Experimental Neurophysiology, Department of Neurology, Ghent University Hospital, 1K12, 185 De Pintelaan, 9000 Ghent, Belgium. Annelies.VanDycke@UGent.be
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MeSH Terms
Descriptor/Qualifier:
Adenosine / administration & dosage*
Adenosine Kinase / deficiency,  genetics
Animals
Astrocytes / cytology,  metabolism,  transplantation*
Blotting, Western
Cell Differentiation
Chromatography, Liquid
Epilepsy / drug therapy*
Female
Fetal Stem Cells / cytology,  metabolism,  transplantation*
Immunohistochemistry
Injections, Intraventricular
Male
Mass Spectrometry
Mice
Mice, Inbred C57BL
Mice, Knockout
Polymerase Chain Reaction
Stem Cell Transplantation / methods*
Grant Support
ID/Acronym/Agency:
MH083973/MH/NIMH NIH HHS; NS057475/NS/NINDS NIH HHS; NS057538/NS/NINDS NIH HHS; NS058780/NS/NINDS NIH HHS; NS061844/NS/NINDS NIH HHS; R01 MH083973/MH/NIMH NIH HHS; R01 MH083973-02/MH/NIMH NIH HHS; R01 MH083973-03/MH/NIMH NIH HHS; R01 MH083973-04/MH/NIMH NIH HHS; R01 NS058780-03/NS/NINDS NIH HHS; R01 NS058780-04/NS/NINDS NIH HHS; R01 NS061844/NS/NINDS NIH HHS; R01 NS061844-02/NS/NINDS NIH HHS; R01 NS061844-03/NS/NINDS NIH HHS; R01 NS061844-04/NS/NINDS NIH HHS; R21 NS057475-01A2/NS/NINDS NIH HHS; R21 NS057538-01A2/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
58-61-7/Adenosine; EC 2.7.1.20/Adenosine Kinase
Comments/Corrections

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