title: Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat.
abstract: Effective transplant-mediated repair of ischemic brain lesions entails extensive tissue remodeling, especially in the ischemic core. Neural stem cells (NSCs) are promising reparative candidates for stroke induced lesions, however, their survival and integration with the host-tissue post-transplantation is poor. In this study, we address this challenge by testing whether co-grafting of NSCs with olfactory ensheathing cells (OECs), a special type of glia with proven neuroprotective, immunomodulatory, and angiogenic effects, can promote graft survival and host tissue remodelling. Transient focal cerebral ischemia was induced in adult rats by a 60-min middle cerebral artery occlusion (MCAo) followed by reperfusion. Ischemic lesions were verified by neurological testing and magnetic resonance imaging. Transplantation into the globus pallidus of NSCs alone or in combination with OECs was performed at two weeks post-MCAo, followed by histological analyses at three weeks post-transplantation. We found evidence of extensive vascular remodelling in the ischemic core as well as evidence of NSC motility away from the graft and into the infarct border in severely lesioned animals co-grafted with OECs. These findings support a possible role of OECs as part of an in situ tissue engineering paradigm for transplant mediated repair of ischemic brain lesions.
authors.affiliation: Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Ingrid Lovise
authors.initials: IL
authors.lastname: Augestad
authors.affiliation: Department of Circulation and Medical Imaging, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Axel Karl Gottfrid
authors.initials: AKG
authors.lastname: Nyman
authors.affiliation: Department of Biotechnology, Faculty of Natural Sciences and Technology, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Alex Ignatius
authors.initials: AI
authors.lastname: Costa
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: Susan Carol
authors.initials: SC
authors.lastname: Barnett
authors.affiliation: Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.|Division of Pharmacology and Clinical Neurosciences, Department of Neurosurgery and Clinical Neurophysiology, Umeå University, Umeå, Sweden.
authors.forename: Axel
authors.initials: A
authors.lastname: Sandvig
authors.affiliation: Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. asta.haberg@ntnu.no.|Department of Radiology and Nuclear Medicine, St. Olavs, Trondheim University Hospital, Trondheim, Norway. asta.haberg@ntnu.no.
authors.forename: Asta Kristine
authors.initials: AK
authors.lastname: Håberg
authors.affiliation: Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Sandvig
mesh_terms: D000367:Age Factors; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D002546:Ischemic Attack, Transient / Q000473:pathology* / Q000628:therapy*; D008297:Male; D058953:Neural Stem Cells / Q000502:physiology / Q000637:transplantation*; D009473:Neuronal Plasticity / Q000502:physiology; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D016896:Treatment Outcome
keywords: CNS regeneration; Stroke; Tissue engineering; Vascular remodeling