Engineering embryonic stem cell derived glia for adenosine delivery.

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.

• Authors: Denise E Fedele, Peter Koch, Louis Scheurer, Elizabeth M Simpson, Hanns Möhler, Oliver Brüstle, Detlev Boison
• Journal: Neuroscience letters (Neurosci Lett) Vol. 370 Issue 2-3 Pg. 160-5 (Nov 11 2004) ISSN: 0304-3940 [Print] Ireland
• PMID: 15488315 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glial Fibrillary Acidic Protein
• Growth Substances
• Intermediate Filament Proteins
• Nerve Tissue Proteins
• Nes protein, mouse
• Nestin
• O Antigens
• Adenosine Kinase
• Adenosine

Topics

• Adenosine (metabolism)
• Adenosine Kinase (deficiency, genetics)
• Analysis of Variance
• Animals
• Blotting, Western (methods)
• Cell Differentiation (drug effects, physiology)
• Cells, Cultured
• Chromosome Mapping (methods)
• Embryo, Mammalian
• Fluorescent Antibody Technique (methods)
• Gene Expression Regulation, Developmental (drug effects)
• Genetic Engineering
• Glial Fibrillary Acidic Protein (immunology)
• Growth Substances (pharmacology)
• Intermediate Filament Proteins (metabolism)
• Mice
• Nerve Tissue Proteins (metabolism)
• Nestin
• Neuroglia (drug effects, metabolism)
• O Antigens (metabolism)
• Oligodendroglia (metabolism)
• Polymerase Chain Reaction (methods)
• Stem Cell Transplantation
• Stem Cells (physiology)