Sporadic ALS Astrocytes Induce Neuronal Degeneration In Vivo

Stem Cell Reports. 2017 Apr 11;8(4):843-855. doi: 10.1016/j.stemcr.2017.03.003. Epub 2017 Mar 30.


Astrocytes from familial amyotrophic lateral sclerosis (ALS) patients or transgenic mice are toxic specifically to motor neurons (MNs). It is not known if astrocytes from sporadic ALS (sALS) patients cause MN degeneration in vivo and whether the effect is specific to MNs. By transplanting spinal neural progenitors, derived from sALS and healthy induced pluripotent stem cells (iPSCs), into the cervical spinal cord of adult SCID mice for 9 months, we found that differentiated human astrocytes were present in large areas of the spinal cord, replaced endogenous astrocytes, and contacted neurons to a similar extent. Mice with sALS but not non-ALS cells showed reduced non-MNs numbers followed by MNs in the host spinal cord. The surviving MNs showed reduced inputs from inhibitory neurons and exhibited disorganized neurofilaments and aggregated ubiquitin. Correspondingly, mice with sALS but not non-ALS cells showed declined movement deficits. Thus, sALS iPSC-derived astrocytes cause ALS-like degeneration in both MNs and non-MNs.

Keywords: amyotrophic lateral sclerosis; astrocytes; cell transplantation; chimera; induced pluripotent stem cells; interneurons; motor neurons; neuron-glial interaction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amyotrophic Lateral Sclerosis / pathology*
  • Animals
  • Astrocytes / pathology*
  • Cell Line
  • Disease Models, Animal
  • Humans
  • Induced Pluripotent Stem Cells / transplantation
  • Male
  • Mice
  • Mice, SCID
  • Motor Neurons / pathology*
  • Neural Stem Cells / pathology
  • Neural Stem Cells / transplantation
  • Spinal Cord / pathology*
  • Synapses / pathology

Supplementary concepts

  • Amyotrophic lateral sclerosis 1