期刊
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
卷 19, 期 7, 页码 390-396出版社
W B SAUNDERS CO LTD
DOI: 10.1016/j.seizure.2010.05.010
关键词
Adenosine; Adenosine kinase; Neural stem cell; Neural progenitor cell; Epilepsy; Local delivery; LC-MS/MS
资金
- Fund for Scientific Research-Flanders
- Ghent University Hospital
- National Institutes of Health (NIH) [NS061844, NS057475, NS058780, NS057538, MH083973]
- Ghent University
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. (C) 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
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