Journal
STEM CELL RESEARCH
Volume 10, Issue 3, Pages 417-427Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.scr.2013.01.009
Keywords
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Funding
- NIH/NINDS [P01NS057778]
- NIH/CHHD [R21HD060899]
- Advancing a Healthier Wisconsin
- ALS Association
- CHDI Foundation, New York
- Quadracci Memorial Fellowship
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We have developed a simple method to generate and expand multipotent, self-renewing pre-rosette neural stem cells from both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs) without utilizing embryoid body formation, manual selection techniques, or complex combinations of small molecules. Human ESC and iPSC colonies were lifted and placed in a neural stem cell medium containing high concentrations of EGF and FGF-2. Cell aggregates (termed EZ spheres) could be expanded for long periods using a chopping method that maintained cell cell contact. Early passage EZ spheres rapidly down-regulated OCT4 and up-regulated SOX2 and nestin expression. They retained the potential to form neural rosettes and consistently differentiated into a range of central and peripheral neural lineages. Thus, they represent a very early neural stem cell with greater differentiation flexibility than other previously described methods. As such, they will be useful for the rapidly expanding field of neurological development and disease modeling, high-content screening, and regenerative therapies based on pluripotent stem cell technology. (C) 2013 Elsevier B.V. All rights reserved.
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