iPSC-derived neural precursors exert a neuroprotective role in immune-mediated demyelination via the secretion of LIF

Nat Commun. 2013;4:2597. doi: 10.1038/ncomms3597.

Abstract

The possibility of generating neural stem/precursor cells (NPCs) from induced pluripotent stem cells (iPSCs) has opened a new avenue of research that might nurture bench-to-bedside translation of cell transplantation protocols in central nervous system myelin disorders. Here we show that mouse iPSC-derived NPCs (miPSC-NPCs)-when intrathecally transplanted after disease onset-ameliorate clinical and pathological features of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Transplanted miPSC-NPCs exert the neuroprotective effect not through cell replacement, but through the secretion of leukaemia inhibitory factor that promotes survival, differentiation and the remyelination capacity of both endogenous oligodendrocyte precursors and mature oligodendrocytes. The early preservation of tissue integrity limits blood-brain barrier damage and central nervous system infiltration of blood-borne encephalitogenic leukocytes, ultimately responsible for demyelination and axonal damage. While proposing a novel mechanism of action, our results further expand the therapeutic potential of NPCs derived from iPSCs in myelin disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cell Movement
  • Cell- and Tissue-Based Therapy / methods*
  • Demyelinating Diseases / immunology
  • Demyelinating Diseases / pathology
  • Demyelinating Diseases / therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / therapy*
  • Female
  • Gene Expression
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / physiology*
  • Injections, Spinal
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Leukemia Inhibitory Factor / genetics*
  • Leukemia Inhibitory Factor / metabolism
  • Mice
  • Mice, Transgenic
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / therapy*
  • Neural Stem Cells / cytology
  • Neural Stem Cells / physiology*
  • Neural Stem Cells / transplantation
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Oligodendroglia / cytology
  • Oligodendroglia / physiology
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism

Substances

  • Biomarkers
  • GKLF protein
  • Kruppel-Like Transcription Factors
  • Leukemia Inhibitory Factor
  • Lif protein, mouse
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse