Human induced pluripotent stem cells are a novel source of neural progenitor cells (iNPCs) that migrate and integrate in the rodent spinal cord

J Comp Neurol. 2014 Aug 15;522(12):2707-28. doi: 10.1002/cne.23578. Epub 2014 Apr 12.


Transplantation of human neural progenitor cells (NPCs) into the brain or spinal cord to replace lost cells, modulate the injury environment, or create a permissive milieu to protect and regenerate host neurons is a promising therapeutic strategy for neurological diseases. Deriving NPCs from human fetal tissue is feasible, although problematic issues include limited sources and ethical concerns. Here we describe a new and abundant source of NPCs derived from human induced pluripotent stem cells (iPSCs). A novel chopping technique was used to transform adherent iPSCs into free-floating spheres that were easy to maintain and were expandable (EZ spheres) (Ebert et al. [2013] Stem Cell Res 10:417-427). These EZ spheres could be differentiated towards NPC spheres with a spinal cord phenotype using a combination of all-trans retinoic acid (RA) and epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) mitogens. Suspension cultures of NPCs derived from human iPSCs or fetal tissue have similar characteristics, although they were not similar when grown as adherent cells. In addition, iPSC-derived NPCs (iNPCs) survived grafting into the spinal cord of athymic nude rats with no signs of overgrowth and with a very similar profile to human fetal-derived NPCs (fNPCs). These results suggest that human iNPCs behave like fNPCs and could thus be a valuable alternative for cellular regenerative therapies of neurological diseases.

Keywords: Human iPS cells; neural progenitor cells; astrocytes; cell transplantation; regenerative therapy; ALS.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Aquaporin 4 / metabolism
  • Astrocytes / physiology
  • Cell Differentiation / physiology*
  • Cell Movement / physiology*
  • Humans
  • Induced Pluripotent Stem Cells / physiology*
  • Ki-67 Antigen / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / physiology*
  • Neural Stem Cells / transplantation
  • Neurons / metabolism
  • Rats
  • Rats, Nude
  • Spinal Cord / cytology*
  • Spinal Cord / surgery
  • Transcriptome / physiology


  • Aquaporin 4
  • Ki-67 Antigen
  • Nerve Tissue Proteins