Functional properties of ES cell-derived neurons engrafted into the hippocampus of adult normal and chronically epileptic rats.
OBJECTIVE
Embryonic stem (ES) cell-based therapy strategies are thought to bear considerable promise in chronic neurologic disorders. Nonetheless, studies addressing the functional properties of ES cell-derived progeny after transplantation into the adult, pathologically modified CNS are scarce.


METHODS
We therefore transplanted ES cell-derived neural precursors expressing enhanced green fluorescent protein only in neuronal progeny bilaterally into the hippocampi of pilocarpine-treated chronically epileptic and sham-control rats. Whole-cell patch-clamp recordings of identified ES cell-derived neurons (ESNs) in hippocampal slices were performed 13 to 34 days after transplantation.


RESULTS
Most ESNs were found in clusters at the transplant site and did not migrate into host tissue. However, they gave rise to a dense network of processes extending over large distances into the host tissue. All ESNs possessed the ability to generate action potentials and expressed voltage-gated Na+ and K+ currents, as well as hyperpolarization-activated currents. Likewise, most ESNs received non-N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid (GABA)A receptor-mediated synaptic input. Both types of synapses displayed intact short-term plasticity. An unusual feature of the majority of ESNs was the occurrence of spontaneous pacemaking activity at frequencies approximately 3 Hertz. No obvious differences were found between the functional properties of ESNs in sham-control and in pilocarpine-treated rats.


CONCLUSIONS
After transplantation into adult control and epileptic rats, ESNs displayed intrinsic and synaptic properties characteristic of neurons. Even though ESNs remained close to the transplant site, the formation of extensive networks of graft-derived processes may be useful for ES cell-based substance delivery.
Rüschenschmidt
Christiane
C
Institute of Reconstructive Neurobiology, University of Bonn Medical Center and Hertie Foundation, Bonn, Germany.
Koch
Peter G
PG
Brüstle
Oliver
O
Beck
Heinz
H
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D002908:Chronic Disease; D018891:Dentate Gyrus / Q000166:cytology; D004827:Epilepsy / Q000139:chemically induced* / Q000601:surgery*; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology / Q000502:physiology* / Q000601:surgery; D066298:In Vitro Techniques; D009474:Neurons / Q000502:physiology* / Q000637:transplantation; D018408:Patch-Clamp Techniques; D019580:Perforant Pathway / Q000502:physiology; D010862:Pilocarpine; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D016875:tau Proteins / Q000502:physiology
D011963:Receptors, GABA-A; D016875:tau Proteins; D010862:Pilocarpine; D049452:Green Fluorescent Proteins