title: Expandable and Rapidly Differentiating Human Induced Neural Stem Cell Lines for Multiple Tissue Engineering Applications.
abstract: 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.
authors: Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
authors: Dana M
authors: DM
authors: Cairns
authors: Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
authors: Karolina
authors: K
authors: Chwalek
authors: Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
authors: Yvonne E
authors: YE
authors: Moore
authors: Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
authors: Matt R
authors: MR
authors: Kelley
authors: Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
authors: Rosalyn D
authors: RD
authors: Abbott
authors: Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
authors: Stephen
authors: S
authors: Moss
authors: Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA. Electronic address: david.kaplan@tufts.edu.
authors: David L
authors: DL
authors: Kaplan
mesh_terms: D000818:Animals; D015415:Biomarkers; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D002642:Chick Embryo; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D033581:Stem Cell Transplantation; D023822:Tissue Engineering / Q000379:methods
chemical_list: D015415:Biomarkers