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Neurosci Lett. 2004 Nov 11;370(2-3):160-5.

Engineering embryonic stem cell derived glia for adenosine delivery.

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Institute of Pharmacology and Toxicology, University of Zürich, CH-8057 Zürich, Switzerland.


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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