title: Therapeutic potential of human induced pluripotent stem cells in experimental stroke.
abstract: Ischemic stroke mainly caused by middle cerebral artery occlusion (MCAo) is a major type of stroke, but there are currently very limited therapeutic options for its cure. Neural stem cells (NSCs) or neural precursor cells (NPCs) derived from various sources are known to survive and improve neurological functions when they are engrafted in animal models of stroke. Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients are novel cells that promise the autologous cell therapy for stroke. In this study, we successfully differentiated iPSCs derived from human fibroblasts into NPCs and found their robust therapeutic potential in a rodent MCAo stroke model. We observed the significant graft-induced behavioral recovery, as well as extensive neural tissue formation. Animal MRI results indicated that the majority of contralaterally transplanted iPSC-derived NPCs migrated to the peri-infarct area, showing a pathotropism critical for tissue recovery. The transplanted animals exhibited the significant reduction of stroke-induced inflammatory response, gliosis and apoptosis, and the contribution to the endogenous neurogenesis. Our results demonstrate that iPSC-derived NPCs are effective cells for the treatment of stroke.
authors.affiliation: CHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seoul, Korea.
authors.forename: Da-Jeong
authors.initials: DJ
authors.lastname: Chang
authors.forename: Nayeon
authors.initials: N
authors.lastname: Lee
authors.forename: In-Hyun
authors.initials: IH
authors.lastname: Park
authors.forename: Chunggab
authors.initials: C
authors.lastname: Choi
authors.forename: Iksoo
authors.initials: I
authors.lastname: Jeon
authors.forename: Jihye
authors.initials: J
authors.lastname: Kwon
authors.forename: Seung-Hun
authors.initials: SH
authors.lastname: Oh
authors.forename: Dong Ah
authors.initials: DA
authors.lastname: Shin
authors.forename: Jeong Tae
authors.initials: JT
authors.lastname: Do
authors.forename: Dong Ryul
authors.initials: DR
authors.lastname: Lee
authors.forename: Hyunseung
authors.initials: H
authors.lastname: Lee
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Moon
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Hong
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
authors.forename: Jihwan
authors.initials: J
authors.lastname: Song
mesh_terms: D000818:Animals; D017209:Apoptosis; D001522:Behavior, Animal; D002454:Cell Differentiation; D002460:Cell Line; D058948:Cell Tracking; D004195:Disease Models, Animal; D005911:Gliosis / Q000473:pathology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000637:transplantation*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D020521:Stroke / Q000209:etiology / Q000473:pathology / Q000628:therapy*