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Ai Z.,Yunnan Key Laboratory of Primate Biomedicine Research | Xiang Z.,Yunnan Key Laboratory of Primate Biomedicine Research | Li Y.,Southwest University | Liu G.,Yunnan Key Laboratory of Primate Biomedicine Research | And 8 more authors.
Biomaterials | Year: 2016

Non-human primates provide optimal models for the development of stem cell therapies. Although somatic cells have been converted into neural stem/progenitor cells, it is unclear whether telencephalic neuroepithelial stem cells (NESCs) with stable properties can be generated from fibroblasts in primate. Here we report that a combination of transcription factors (Oct4, Sox2, Klf4) with a new culture medium induces rhesus monkey fibroblasts into NESCs, which can develop into miniature neural tube (NT)-like structures at a cell level. Furthermore, single induced NESCs (iNESCs) can generate later-stage 3D-NTs after grown on matrigel in suspension culture. iNESCs express NT cell markers, have a unique gene expression pattern biasing towards telencephalic patterning, and give rise to cortical neurons. Via transplantation, single iNESCs can extensively survive, regenerate myelinated neuron axons and synapse structures in adult monkey striatum and cortex, and differentiate into cortical neurons. Successful transplantation is closely associated with graft regions and grafted cell identities. The ability to generate defined and transplantable iNESCs from primate fibroblasts under a defined condition with predictable fate choices will facilitate disease modeling and cell therapy. © 2015 Elsevier Ltd.


The present invention discloses a culture medium for establishing neuroepithelial stem cells, a method for establishing neuroepithelial stem cells, and the applications thereof, wherein the culture medium comprises differentiation culture medium for inducing and differentiating pluripotent stem cells to elementary neuroepithelial stem cells as well as proliferation culture medium for amplifying the elementary neuroepithelial stem cells; and the pluripotent stem cells can be differentiated to the elementary neuroepithelial stem cells in the differentiation culture medium. While the elementary neuroepithelial stem cells have the functions of the neuroepithelial stem cells, they cannot be stably amplified in long term culture under the conventional culture conditions, however they are maintained the stability properties in long term culture in the proliferation culture medium. The proliferation culture medium can culture the elementary neuroepithelial stem cells to the neuroepithelial stem cells, which are maintained stable amplification and survival, and can be produced in large scale.

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