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Engineering embryonic stem cell derived glia for adenosine delivery.

Denise E Fedele1, Peter Koch, Louis Scheurer

  • 1Institute of Pharmacology and Toxicology, University of Zürich, CH-8057 Zürich, Switzerland.

Neuroscience Letters
|October 19, 2004
PubMed
Summary

Adenosine releasing stem cells show promise for epilepsy treatment. Genetically modified embryonic stem cells lacking adenosine kinase can differentiate into glial cells that release therapeutic levels of adenosine, potentially suppressing seizures.

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Area of Science:

  • Neuroscience
  • Stem Cell Biology
  • Biochemistry

Background:

  • Adenosine exhibits anticonvulsant and neuroprotective effects.
  • Embryonic stem (ES) cells offer potential for cell transplantation due to pluripotency and self-renewal.
  • Epilepsy treatment could benefit from novel stem cell-based adenosine delivery systems.

Purpose of the Study:

  • To assess the feasibility of using stem cells for adenosine delivery.
  • To generate adenosine-releasing stem cells for potential epilepsy therapy.

Main Methods:

  • Disruption of both adenosine kinase (ADK) alleles in ES cells using homologous recombination.
  • Differentiation of Adk-/- ES cells into glial precursors, astrocytes, and oligodendrocytes.
  • Quantification of adenosine release from differentiated Adk-/- ES cell-derived glial populations.

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Main Results:

  • Adk-/- ES cells successfully differentiated into glial lineages without compromising potential.
  • Glial cells derived from Adk-/- ES cells released significant amounts of adenosine (up to 40.1 +/- 6.0 ng/10^5 cells/hour).
  • This adenosine release level is considered sufficient for seizure suppression.

Conclusions:

  • A lack of ADK does not impede glial differentiation in ES cells.
  • Adk-/- ES cells represent a viable source for generating therapeutic adenosine-releasing grafts.
  • These modified stem cells hold potential as a novel treatment strategy for epilepsy.