Embryonic neural stem cells transplanted in middle cerebral artery occlusion model of rats demonstrated potent therapeutic effects, compared to adult neural stem cells.
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.
Takahashi
Kazuya
K
Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
Yasuhara
Takao
T
Shingo
Tetsuro
T
Muraoka
Kenichiro
K
Kameda
Masahiro
M
Takeuchi
Akira
A
Yano
Akimasa
A
Kurozumi
Kazuhiko
K
Agari
Takashi
T
Miyoshi
Yasuyuki
Y
Kinugasa
Kazushi
K
Date
Isao
I
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
D051100:Glial Cell Line-Derived Neurotrophic Factor; D049408:Luminescent Agents; D049452:Green Fluorescent Proteins