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Engineering embryonic stem cell derived glia for adenosine delivery.

Denise E Fedele·Peter Koch·Louis Scheurer·Elizabeth M Simpson·Hanns Möhler·Oliver Brüstle·Detlev Boison
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Abstract

Based on the anticonvulsant and neuroprotective properties of adenosine, and based on the long-term survival potential of stem cell derived brain implants, adenosine releasing stem cells may constitute a novel tool for the treatment of epilepsy. Pluripotency and unlimited self-renewal make embryonic stem (ES) cells a particularly versatile donor source for cell transplantation. With the aim to test the feasibility of a stem cell-based delivery system for adenosine, both alleles of adenosine kinase (ADK), the major adenosine-metabolizing enzyme, were disrupted by homologous recombination in ES cells. Adk-/- ES cells were subjected to a glial differentiation protocol and, as a result, gave rise to proliferating glial precursors, which could be further differentiated into mature astrocytes and oligodendrocytes. Thus, a lack of ADK does not compromise the glial differentiation potential of ES cells. The Adk-/- ES cells yielded glial populations with an adenosine release of up to 40.1 +/- 6.0 ng per 10(5) cells per hour, an amount considered to be sufficient for seizure suppression. Our findings indicate that Adk-/- ES cells constitute a potential source for therapeutic adenosine releasing grafts.

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AdenosineAdenosine KinaseAnalysis of VarianceAnimalsBlotting, WesternCell DifferentiationCells, CulturedChromosome MappingEmbryo, MammalianFluorescent Antibody TechniqueGene Expression Regulation, DevelopmentalGenetic EngineeringGlial Fibrillary Acidic ProteinGrowth SubstancesIntermediate Filament ProteinsMiceNerve Tissue ProteinsNestinNeurogliaO AntigensOligodendrogliaPolymerase Chain ReactionStem Cell TransplantationStem CellsComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't

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Denise E Fedele, Peter Koch, Louis Scheurer, Elizabeth M Simpson, Hanns Möhler, Oliver Brüstle, Detlev Boison. 2004-11-11. Engineering embryonic stem cell derived glia for adenosine delivery.. https://doi.org/10.1016/j.neulet.2004.08.031

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