title: Human neural progenitor cells show functional neuronal differentiation and regional preference after engraftment onto hippocampal slice cultures.
abstract: The transplantation of stem cells offers potential therapies for many neurodegenerative disorders that currently have limited or no treatment options. However, relatively little is known about how the host environment affects the development and integration of these cells. In this study we have engrafted immortalized human midbrain neural progenitor cells (NPCs) onto rat hippocampal brain slice cultures to examine the influence of a neural environment on differentiation. Patch clamp recordings revealed that the transplanted progenitor cells could express neuronal-type voltage-gated currents and rapidly receive synaptic input from the hippocampal brain slice. The distribution of progenitor cells across the hippocampal slices was strongly influenced by the neural architecture, with most cells located in the fissural regions and sending processes parallel to the laminar structure, while in contrast, cells located in the dentate gyrus showed no organized pattern. Almost no cells were found in the stratum radiatum or pyramidal cell layers. Together, these results demonstrate the potential for the architecture of the host environment to regulate the integration of transplanted cells, and highlight the utility of coculture systems for studying the mechanisms underlying the migration, integration, and differentiation of human NPCs in structured neural environments.
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Morgan
authors.forename: Andrea
authors.initials: A
authors.lastname: Liedmann
authors.forename: Rayk
authors.initials: R
authors.lastname: Hübner
authors.forename: Marine
authors.initials: M
authors.lastname: Hovakimyan
authors.forename: Arndt
authors.initials: A
authors.lastname: Rolfs
authors.forename: Moritz J
authors.initials: MJ
authors.lastname: Frech
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002461:Cell Line, Transformed; D018920:Coculture Techniques; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D055153:Stem Cell Niche / Q000502:physiology*; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous