Stem Cell Reports
Volume 7, Issue 3, 13 September 2016, Pages 557-570
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Expandable and Rapidly Differentiating Human Induced Neural Stem Cell Lines for Multiple Tissue Engineering Applications

https://doi.org/10.1016/j.stemcr.2016.07.017Get rights and content
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Highlights

  • Human induced neural stem cell (hiNSC) lines can be passaged and cryopreserved

  • Rapid and robust media-independent differentiation in as few as 4 days

  • hiNSCs contribute to both central and peripheral nervous systems in vivo

  • Demonstration of utility in innervated muscle co-culture and 3D human brain model

Summary

Limited availability of human neurons poses a significant barrier to progress in biological and preclinical studies of the human nervous system. Current stem cell-based approaches of neuron generation are still hindered by prolonged culture requirements, protocol complexity, and variability in neuronal differentiation. Here we establish stable human induced neural stem cell (hiNSC) lines through the direct reprogramming of neonatal fibroblasts and adult adipose-derived stem cells. These hiNSCs can be passaged indefinitely and cryopreserved as colonies. Independently of media composition, hiNSCs robustly differentiate into TUJ1-positive neurons within 4 days, making them ideal for innervated co-cultures. In vivo, hiNSCs migrate, engraft, and contribute to both central and peripheral nervous systems. Lastly, we demonstrate utility of hiNSCs in a 3D human brain model. This method provides a valuable interdisciplinary tool that could be used to develop drug screening applications as well as patient-specific disease models related to disorders of innervation and the brain.

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