title: Conditionally immortalised neural stem cells promote functional recovery and brain plasticity after transient focal cerebral ischaemia in mice.
abstract: Cell therapy has enormous potential to restore neurological function after stroke. The present study investigated effects of conditionally immortalised neural stem cells (ciNSCs), the Maudsley hippocampal murine neural stem cell line clone 36 (MHP36), on sensorimotor and histological outcome in mice subjected to transient middle cerebral artery occlusion (MCAO). Adult male C57BL/6 mice underwent MCAO by intraluminal thread or sham surgery and MHP36 cells or vehicle were implanted into ipsilateral cortex and caudate 2 days later. Functional recovery was assessed for 28 days using cylinder and ladder rung tests and tissue analysed for plasticity, differentiation and infarct size. MHP36-implanted animals showed accelerated and augmented functional recovery and an increase in neurons (MAP-2), synaptic plasticity (synaptophysin) and axonal projections (GAP-43) but no difference in astrocytes (GFAP), oligodendrocytes (CNPase), microglia (IBA-1) or lesion volumes when compared to vehicle group. This is the first study showing a potential functional benefit of the ciNSCs, MHP36, after focal MCAO in mice, which is probably mediated by promoting neuronal differentiation, synaptic plasticity and axonal projections and opens up opportunities for future exploitation of genetically altered mice for dissection of mechanisms of stem cell based therapy.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK.
authors.forename: Shalmali
authors.initials: S
authors.lastname: Patkar
authors.forename: Rothwelle
authors.initials: R
authors.lastname: Tate
authors.forename: Michel
authors.initials: M
authors.lastname: Modo
authors.forename: Robin
authors.initials: R
authors.lastname: Plevin
authors.forename: Hilary V O
authors.initials: HV
authors.lastname: Carswell
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal; D020520:Brain Infarction / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D002461:Cell Line, Transformed; D002546:Ischemic Attack, Transient / Q000150:complications / Q000503:physiopathology* / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology*; D033581:Stem Cell Transplantation; D013569:Synapses / Q000378:metabolism / Q000473:pathology