title: Focal transplantation of human iPSC-derived glial-rich neural progenitors improves lifespan of ALS mice.
abstract: Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1)-mediated amyotrophic lateral sclerosis (ALS). However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source.
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; CREST, JST, Saitama 332-0012, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; CREST, JST, Saitama 332-0012, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Funayama
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; CREST, JST, Saitama 332-0012, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Tsukita
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; CREST, JST, Saitama 332-0012, Japan; PRESTO, JST, Saitama 332-0012, Japan; iCeMS, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Akitsu
authors.initials: A
authors.lastname: Hotta
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors.forename: Akimasa
authors.initials: A
authors.lastname: Yasuda
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nori
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo 160-8582, Japan; Department of Orthopaedic Surgery, National Hospital Organization, Murayama Medical Center, Tokyo 208-0011, Japan.
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Department of Physiology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamanaka
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; CREST, JST, Saitama 332-0012, Japan. Electronic address: haruhisa@cira.kyoto-u.ac.jp.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D004195:Disease Models, Animal; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D053208:Kaplan-Meier Estimate; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: D009414:Nerve Growth Factors; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt