title: Functional recovery of the murine brain ischemia model using human induced pluripotent stem cell-derived telencephalic progenitors.
abstract: Induced pluripotent stem (iPS) cells possess the properties of self-renewal and pluripotency, similar to embryonic stem cells. They are a good candidate as a source of suitable cells for cell replacement therapy. In this study, we transplanted human iPS cell-derived neural progenitors into an ischemic mouse brain. Human iPS cells were differentiated into neuronal progenitors by serum-free culture of embryoid body-like aggregates (SFEBs). Focal cerebral ischemia was induced by occluding the middle cerebral artery using the intraluminal filament technique. Donor cells were transplanted into the ischemic lateral striatum 1 week after ischemia induction. Cells survived at the transplantation site, with migration of a proportion of cells along the external capsule and corpus callosum. Cells that were positive for the basal telencephalon marker, Nkx2.1, migrated into the basal part of the telencephalon. The pallial telencephalon marker, Emx1, was detected in cells that had migrated into the pallial part of the telencephalon. SFEBs differentiated into various types of neurons, and a retrograde tracer labeling study showed that differentiated cells integrated into host neural circuitry. Behavioral recovery was significantly enhanced in the transplanted group. Our results suggest that human iPS cell-derived neuronal progenitors survive and migrate in the ischemic brain, and contribute toward functional recovery via neural circuit reconstitution.
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Gomi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takagi
authors.forename: Asuka
authors.initials: A
authors.lastname: Morizane
authors.forename: Daisuke
authors.initials: D
authors.lastname: Doi
authors.forename: Masaki
authors.initials: M
authors.lastname: Nishimura
authors.forename: Susumu
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002545:Brain Ischemia / Q000175:diagnosis / Q000601:surgery*; D002454:Cell Differentiation; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D005136:Eye Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D017078:Laser-Doppler Flowmetry; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D050811:Octamer Transcription Factor-1 / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D012039:Regional Blood Flow; D012097:Repressor Proteins / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D012720:Severity of Illness Index; D033581:Stem Cell Transplantation / Q000379:methods*; D013266:Stilbamidines; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014404:Tubulin / Q000378:metabolism
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D005136:Eye Proteins; C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D050811:Octamer Transcription Factor-1; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; C098693:Sox1 protein, mouse; D013266:Stilbamidines; D014404:Tubulin; C462941:beta3 tubulin, mouse