Astrocytes derived from fetal neural progenitor cells as a novel source for therapeutic adenosine delivery

Annelies Van Dycke, Robrecht Raedt, Alain Verstraete, Panos Theofilas, Wytse Wadman, Kristl Vonck, Detlev Boison, Paul Boon

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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 105 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 105 cells) compared to wild-type cells (3 ± 0.2 ng per 105 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.

Original languageEnglish (US)
Pages (from-to)390-396
Number of pages7
JournalSeizure
Volume19
Issue number7
DOIs
StatePublished - Sep 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Keywords

  • Adenosine
  • Adenosine kinase
  • Epilepsy
  • LC-MS/MS
  • Local delivery
  • Neural progenitor cell
  • Neural stem cell

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