Timely, Efficient Neural Conversion of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells

SK1408

Summary of Invention

The synergistic action of two inhibitors of SMAD signaling, Noggin (or the BMP inhibitor dorsomorphin) and SB431542, is sufficient for inducing rapid and complete conversion of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) under adherent culture conditions into neural cells. Studies indicate neural induction in as little as five days, and differentiation into central nervous system subtypes (including midbrain dopamine neurons and spinal motoneurons) in less than 20 days. By changes in cell density and timing of Noggin application, further ectoderm lineages including neural tube floor plate, neural crest, and structures originating from anterior placodes (eye lens, otic cells, olfactory epithelium, and trigeminal neurons) can be obtained.

This platform allows for large numbers of cells to be generated for the study of early human development, disease modeling, drug discovery, and applications in regenerative medicine.

Advantages

Current widely utilized neural protocols in human ES cells rely on embryoid body formation, stromal feeder co-culture, or selective survival conditions; each strategy displays significant drawbacks such as poorly defined culture conditions, protracted differentiation, and low yield. This newly defined Noggin/SB431542-based neural induction method will:

  • Facilitate the use of hESCs and hiPSCs in a research setting
  • Obviate the need for stromal feeder or embryoid body based protocols
  • Result in an accelerated, highly efficient, cost-effective method for neural conversion

Areas of Application

Method for efficient induction of hESCs or hiPSCs into neural cells

Stage of Development

  • Demonstration of proof of concept
  • Ready for use as a research tool

Lead Inventors

Patent information

  • PCT application published: WO2010/096496
  • U.S. national stage application pending

References

Chambers SM, et al. (2009) Nat Biotechnol Mar; 27(3): 275-80

  • Technology featured in BioCentury in March 2009.

Contact Information

Imke Ehlers, PhD, CLP
Tel. 646-888-1074; Fax: 646-888-1120

E-mail: ehlersi@mskcc.org