Functional network integration of embryonic stem cell-derived astrocytes in hippocampal slice cultures.
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.
Scheffler
Björn
B
Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany.
Schmandt
Tanja
T
Schröder
Wolfgang
W
Steinfarz
Barbara
B
Husseini
Leila
L
Wellmer
Jörg
J
Seifert
Gerald
G
Karram
Khalad
K
Beck
Heinz
H
Blümcke
Ingmar
I
Wiestler
Otmar D
OD
Steinhäuser
Christian
C
Brüstle
Oliver
O
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D017629:Gap Junctions / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D009457:Neuroglia / Q000378:metabolism; D018408:Patch-Clamp Techniques