title: Adult neural progenitor cell grafts survive after acute spinal cord injury and integrate along axonal pathways.
abstract: The main rationale for cell-based therapies following spinal cord injury are: (i) replacement of degenerated spinal cord parenchyma by an axon growth supporting scaffold; (ii) remyelination of regenerating axons; and (iii), local delivery of growth promoting molecules. A potential source to meet these requirements is adult neural progenitor cells, which were examined in the present study. Fibroblast growth factor 2-responsive adult spinal cord-derived syngenic neural progenitor cells were either genetically modified in vitro to express green fluorescent protein (GFP) using retroviral vectors or prelabelled with bromodeoxyuridine (BrdU). Neural progenitor cells revealed antigenic properties of neurons and glial cells in vitro confirming their multipotency. This differentiation pattern was unaffected by retroviral transduction. GFP-expressing or BrdU-prelabelled neural progenitor cells were grafted as neurospheres directly into the acutely injured rat cervical spinal cord. Animals with lesions only served as controls. Three weeks postoperatively, grafted neural progenitor cells integrated along axonal profiles surrounding the lesion site. In contrast to observations in culture, grafted neural progenitor cells differentiated only into astro- and oligodendroglial lineages, supporting the notion that the adult spinal cord provides molecular cues for glial, but not for neuronal, differentiation. This study demonstrates that adult neural progenitor cells will survive after transplantation into the acutely injured spinal cord. The observed oligodendroglial and astroglial differentiation and integration along axonal pathways represent important prerequisites for potential remyelination and support of axonal regrowth.
authors.affiliation: Department of Neurology, University of Regensburg, Universitätsstrasse 84, 93053 Regensburg, Germany.
authors.forename: Maurice
authors.initials: M
authors.lastname: Vroemen
authors.forename: Ludwig
authors.initials: L
authors.lastname: Aigner
authors.forename: Juergen
authors.initials: J
authors.lastname: Winkler
authors.forename: Norbert
authors.initials: N
authors.lastname: Weidner
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000235:genetics; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000637:transplantation*; D009836:Oligodendroglia / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000166:cytology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000601:surgery*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D014161:Transduction, Genetic
chemical_list: D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins