Neuroprotection in ischemic mouse brain induced by stem cell-derived brain implants.

Abstract

Protective mechanisms of the brain may reduce the extent of injury after focal cerebral ischemia. Here, we explored in a mouse model of focal cerebral ischemia potential synergistic neuroprotective effects of two mediators of neuroprotection: (i) neuronal or glial precursor cells and (ii) the inhibitory neuromodulator adenosine. Embryonic stem (ES) cells, engineered to release adenosine by biallelic disruption of the adenosine kinase gene, and respective wild-type cells were induced to differentiate into either neural or glial precursor cells and were injected into the striatum of mice 1 week before middle cerebral artery occlusion. All stem cell-derived graft recipients were characterized by a significant reduction in infarct volume, an effect that was augmented by the release of adenosine. Neuroprotection was strongest in adenosine-releasing glial precursor cell recipients, which were characterized by an 85% reduction of the infarct area. Graft-mediated neuroprotection correlated with a significant improvement of general and focal neurologic scores. Histologic analysis before and after ischemia revealed clusters of implanted cells within the striatum of all treated mice. We conclude that ES cell derived adenosine-releasing brain implants provide neuroprotection by synergism of endogenous precursor cell-mediated effects and paracrine adenosine release.

• Authors: Giuseppe Pignataro, Francesca E Studer, Andrew Wilz, Roger P Simon, Detlev Boison
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 27 Issue 5 Pg. 919-27 (May 2007) ISSN: 0271-678X [Print] United States
• PMID: 17119544 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine Kinase
• Adenosine

Topics

• Adenosine (metabolism)
• Adenosine Kinase (genetics, physiology)
• Alleles
• Animals
• Brain Ischemia (therapy)
• Cerebral Infarction (pathology, prevention & control)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Nervous System Diseases (pathology, physiopathology)
• Neurons (metabolism, transplantation)
• Stem Cell Transplantation