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.

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