Focal transplantation of human iPSC-derived glial-rich neural progenitors improves lifespan of ALS mice

Takayuki Kondo; Misato Funayama; Kayoko Tsukita; Akitsu Hotta; Akimasa Yasuda; Satoshi Nori; Shinjiro Kaneko; Masaya Nakamura; Ryosuke Takahashi; Hideyuki Okano; Shinya Yamanaka; Haruhisa Inoue

doi:10.1016/j.stemcr.2014.05.017

Focal transplantation of human iPSC-derived glial-rich neural progenitors improves lifespan of ALS mice

Stem Cell Reports. 2014 Aug 12;3(2):242-9. doi: 10.1016/j.stemcr.2014.05.017. Epub 2014 Jun 26.

Authors

Affiliations

¹ 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.
² Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; CREST, JST, Saitama 332-0012, Japan.
³ 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.
⁴ Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo 160-8582, Japan.
⁵ 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.
⁶ Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
⁷ Department of Physiology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
⁸ Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
⁹ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyotrophic Lateral Sclerosis / mortality
Amyotrophic Lateral Sclerosis / pathology
Amyotrophic Lateral Sclerosis / therapy*
Animals
Astrocytes / cytology
Astrocytes / metabolism
Cell Differentiation
Disease Models, Animal
Humans
Induced Pluripotent Stem Cells / cytology*
Kaplan-Meier Estimate
Mice
Mice, Transgenic
Nerve Growth Factors / metabolism
Neural Stem Cells / cytology
Neural Stem Cells / metabolism
Neural Stem Cells / transplantation*
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction
Spinal Cord / pathology
Superoxide Dismutase / genetics
Superoxide Dismutase / metabolism
Transplantation, Heterologous
Up-Regulation

Substances

Nerve Growth Factors
Superoxide Dismutase
Proto-Oncogene Proteins c-akt

Supplementary concepts

Amyotrophic lateral sclerosis 1