title: Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury.
abstract: Various types of induced pluripotent stem (iPS) cells have been established by different methods, and each type exhibits different biological properties. Before iPS cell-based clinical applications can be initiated, detailed evaluations of the cells, including their differentiation potentials and tumorigenic activities in different contexts, should be investigated to establish their safety and effectiveness for cell transplantation therapies. Here we show the directed neural differentiation of murine iPS cells and examine their therapeutic potential in a mouse spinal cord injury (SCI) model. "Safe" iPS-derived neurospheres, which had been pre-evaluated as nontumorigenic by their transplantation into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse brain, produced electrophysiologically functional neurons, astrocytes, and oligodendrocytes in vitro. Furthermore, when the safe iPS-derived neurospheres were transplanted into the spinal cord 9 d after contusive injury, they differentiated into all three neural lineages without forming teratomas or other tumors. They also participated in remyelination and induced the axonal regrowth of host 5HT(+) serotonergic fibers, promoting locomotor function recovery. However, the transplantation of iPS-derived neurospheres pre-evaluated as "unsafe" showed robust teratoma formation and sudden locomotor functional loss after functional recovery in the SCI model. These findings suggest that pre-evaluated safe iPS clone-derived neural stem/progenitor cells may be a promising cell source for transplantation therapy for SCI.
authors.affiliation: Department of Physiology, School of Medicine, Keio University, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Osahiko
authors.initials: O
authors.lastname: Tsuji
authors.forename: Kyoko
authors.initials: K
authors.lastname: Miura
authors.forename: Yohei
authors.initials: Y
authors.lastname: Okada
authors.forename: Kanehiro
authors.initials: K
authors.lastname: Fujiyoshi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Mukaino
authors.forename: Narihito
authors.initials: N
authors.lastname: Nagoshi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kitamura
authors.forename: Gentaro
authors.initials: G
authors.lastname: Kumagai
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishino
authors.forename: Shuta
authors.initials: S
authors.lastname: Tomisato
authors.forename: Hisanobu
authors.initials: H
authors.lastname: Higashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nagai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Katoh
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Kohda
authors.forename: Yumi
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Michisuke
authors.initials: M
authors.lastname: Yuzaki
authors.forename: Eiji
authors.initials: E
authors.lastname: Ikeda
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamanaka
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000637:transplantation; D001369:Axons / Q000473:pathology / Q000637:transplantation; D002454:Cell Differentiation / Q000502:physiology; D017690:Cell Transplantation; D002478:Cells, Cultured; D005260:Female; D057026:Induced Pluripotent Stem Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000473:pathology / Q000637:transplantation; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D020127:Recovery of Function / Q000502:physiology; D012038:Regeneration; D013116:Spinal Cord / Q000166:cytology / Q000601:surgery / Q000637:transplantation; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology* / Q000601:surgery; D013234:Stem Cells / Q000473:pathology