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. 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
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. 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Authors: Denise E Fedele; Peter Koch; Louis Scheurer; Elizabeth M Simpson; Hanns Möhler; Oliver Brüstle; Detlev Boison Journal: Neurosci Lett Date: 2004-11-11 Impact factor: 3.046
Authors: Edwin K Jackson; Shawn E Kotermanski; Elizabeth V Menshikova; Raghvendra K Dubey; Travis C Jackson; Patrick M Kochanek Journal: J Neurochem Date: 2017-04-06 Impact factor: 5.372