title: Transplantation of telencephalic neural progenitors induced from embryonic stem cells into subacute phase of focal cerebral ischemia.
abstract: Cerebral ischemia causes neuronal death and disruption of neural circuits in the central nervous system. Various neurological disorders caused by cerebral infarction can severely impair quality of life and are potentially fatal. Functional recovery in the chronic stage mainly depends on physical treatment and rehabilitation. We aim to establish cell therapy for cerebral ischemia using embryonic stem (ES) cells, which have self-renewing and pluripotent capacities. We previously reported that the transplanted monkey and mouse ES cell-derived neural progenitors, by stromal cell-derived inducing activity method, could survive and differentiate into various types of neurons and glial cells, and form the neuronal network in basal ganglia. In this report, we induced the differentiation of the neural progenitors from mouse ES cells using the serum-free suspension culture method and confirmed the expression of various basal ganglial neuronal markers and neurotransmitter-related markers both in vitro and in vivo, which was thought to be suitable for replacing damaged striatum after middle cerebral artery occlusion. This is the first report that used selectively induced telencephalic neural progenitors into ischemia model. Furthermore, we purified the progenitors expressing the neural progenitor marker Sox1 by fluorescence-activated cell sorting and Sox1-positive neural progenitors prevented tumor formation in ischemic brain for 2 months. We also analyzed survival and differentiation of transplanted cells and functional recovery from ischemic damage.
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takagi
authors.forename: Makoto
authors.initials: M
authors.lastname: Hayase
authors.forename: Takeshi
authors.initials: T
authors.lastname: Marumo
authors.forename: Masanori
authors.initials: M
authors.lastname: Gomi
authors.forename: Masaki
authors.initials: M
authors.lastname: Nishimura
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Kataoka
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nozaki
authors.forename: Susumu
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000166:cytology*; D002545:Brain Ischemia / Q000628:therapy*; D001932:Brain Neoplasms / Q000517:prevention & control; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D016895:Culture Media, Serum-Free; D053595:Embryonic Stem Cells / Q000502:physiology / Q000637:transplantation*; D005434:Flow Cytometry; D051379:Mice; D058953:Neural Stem Cells / Q000502:physiology / Q000637:transplantation; D009460:Neurologic Examination; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013724:Teratoma / Q000517:prevention & control
chemical_list: D016895:Culture Media, Serum-Free; D055748:SOXB1 Transcription Factors; C098693:Sox1 protein, mouse