Long-term self-renewable feeder-free human induced pluripotent stem cell-derived neural progenitors

Stem Cells Dev. 2011 Mar;20(3):503-14. doi: 10.1089/scd.2010.0143. Epub 2010 Dec 2.

Abstract

Human induced pluripotent stem cells (hiPSCs) have led to an important revolution in stem cell research and regenerative medicine. To create patient-specific neural progenitors (NPs), we have established a homogenous, expandable, and self-renewable population of multipotent NPs from hiPSCs, using an adherent system and defined medium supplemented with a combination of factors. The established hiPSC-NPs highly expressed Nestin and Sox1. These NPs were continuously propagated for ~1 year without losing their potential to generate astrocytes, oligodendrocytes, and functional neurons and maintained a stable chromosome number. Voltage clamp analysis revealed outward potassium currents in hiPSC-NPs. The self-renewal characteristic of the NPs was demonstrated by a symmetrical mode of Nestin-positive cell division. Additionally, these hiPSC-NPs can be easily frozen and thawed in the presence of Rho-associated kinase (ROCK) inhibitor without losing their proliferation, karyotype stability, and developmental potential. The characteristics of our generated hiPSC-NPs provide the opportunity to use patient-specific or ready-to-use hiPSC-NPs in future biomedical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism
  • Calcium Channel Blockers / pharmacology
  • Cell Culture Techniques
  • Cell Differentiation
  • Cell Line
  • Cell Shape
  • Cryopreservation
  • Gene Expression Profiling
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / physiology
  • Intermediate Filament Proteins / metabolism
  • Lidocaine / analogs & derivatives
  • Lidocaine / pharmacology
  • Membrane Potentials / drug effects
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Neural Stem Cells / cytology*
  • Neurons / cytology
  • Nifedipine / pharmacology
  • Potassium Channel Blockers / pharmacology
  • SOXB1 Transcription Factors / metabolism
  • Tetraethylammonium / pharmacology
  • Transcription, Genetic

Substances

  • Antigens, Differentiation
  • Calcium Channel Blockers
  • Intermediate Filament Proteins
  • NES protein, human
  • Nerve Tissue Proteins
  • Nestin
  • Potassium Channel Blockers
  • SOX1 protein, human
  • SOXB1 Transcription Factors
  • QX-314
  • Tetraethylammonium
  • Lidocaine
  • Nifedipine