title: Embryonic neural stem cells transplanted in middle cerebral artery occlusion model of rats demonstrated potent therapeutic effects, compared to adult neural stem cells.
abstract: Cell therapy using stem cells is awaited by stroke patients with impaired movement and cognitive functions, although intravenous alteplase-administration ameliorated outcomes of patients receiving the therapy within 3 h of onset. In this study, we explored the therapeutic effects of neural progenitor cells (NPC) upon middle cerebral artery occlusion (MCAO) model of rats with exploration of the differences between adult and embryonic NPCs in therapeutic effects. GFP-labeled adult or embryonic NPCs were transplanted for transient MCAO model of rats at 1h after reperfusion. Rats were examined behaviorally using limb placement test, rotarod test and cylinder test with neuroradiological assessment using magnetic resonance imaging (MRI). Consequently after euthanasia, rats were immunohistochemically investigated to explore graft survival and immune reaction. MRI of rats receiving NPCs revealed significant reduction of infarct volumes, compared to vehicle-treated rats with corresponding behavioral amelioration. The transplanted cells were surviving in rats receiving NPCs, although the number of embryonic NPCs was significantly higher than that of adult NPCs. Iba-1-positive inflammatory cells of rats receiving adult NPCs were prominent, compared to those receiving embryonic NPCs, which might be a rationale for the differences between rats receiving adult and embryonic NPCs in the number of surviving NPCs. On the contraries, adult NPCs surely demonstrated therapeutic effects with a few surviving cells, thus indicating that the therapeutic effects might be due to trophic/growth factor-secretion from transplanted NPCs, rather than replacement of damaged host neurons. Therapeutic effects of NPCs for MCAO model of rats were clarified in this study. Transplantation of NPCs will be a hopeful strategy for stroke patients, although further studies are required for the patient safety and underlying mechanisms.
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Takahashi
authors.forename: Takao
authors.initials: T
authors.lastname: Yasuhara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shingo
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Muraoka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kameda
authors.forename: Akira
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Akimasa
authors.initials: A
authors.lastname: Yano
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kurozumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Agari
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Kazushi
authors.initials: K
authors.lastname: Kinugasa
authors.forename: Isao
authors.initials: I
authors.lastname: Date
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000637:transplantation*; D004797:Enzyme-Linked Immunosorbent Assay; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D049408:Luminescent Agents; D008297:Male; D017628:Microglia / Q000502:physiology; D020768:Middle Cerebral Artery / Q000166:cytology / Q000502:physiology*; D009068:Movement / Q000502:physiology; D009474:Neurons / Q000637:transplantation*; D004856:Postural Balance / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D049408:Luminescent Agents; D049452:Green Fluorescent Proteins