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First published online October 6, 2003
doi: 10.1242/10.1242/dev.00714

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Development 130, 5533-5541 (2003)
Copyright © 2003 The Company of Biologists Limited

RESEARCH ARTICLE: DEVELOPMENT AND DISEASE

Functional network integration of embryonic stem cell-derived astrocytes in hippocampal slice cultures

Björn Scheffler1,*, Tanja Schmandt1,2, Wolfgang Schröder3, Barbara Steinfarz1,2, Leila Husseini3, Jörg Wellmer4, Gerald Seifert3, Khalad Karram1,2, Heinz Beck4, Ingmar Blümcke1, Otmar D. Wiestler1, Christian Steinhäuser3 and Oliver Brüstle1,2,{dagger}

1 Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany
2 Institute of Reconstructive Neurobiology, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany
3 Department of Neurosurgery, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany
4 Department of Epileptology, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany

{dagger} Author for correspondence (e-mail: brustle{at}uni-bonn.de)

Accepted 9 July 2003

Embryonic stem (ES) cells provide attractive prospects for neural transplantation. So far, grafting strategies in the CNS have focused mainly on neuronal replacement. Employing a slice culture model, we found that ES cell-derived glial precursors (ESGPs) possess a remarkable capacity to integrate into the host glial network. Following deposition on the surface of hippocampal slices, ESGPs actively migrate into the recipient tissue and establish extensive cell-cell contacts with recipient glia. Gap junction-mediated coupling between donor and host astrocytes permits widespread delivery of dye from single donor cells. During maturation, engrafted donor cells display morphological, immunochemical and electrophysiological properties that are characteristic of differentiating native glia. Our findings provide the first evidence of functional integration of grafted astrocytes, and depict glial network integration as a potential route for widespread transcellular delivery of small molecules to the CNS.

Key words: ES cells, Glia, Electrophysiology, Gap junction, Hippocampus, Slice culture




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© The Company of Biologists Ltd 2003