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Cells 2018, 7(10), 173; https://doi.org/10.3390/cells7100173

Subcutaneous Maturation of Neural Stem Cell-Loaded Hydrogels Forms Region-Specific Neuroepithelium

1
Integrated Bioscience Program, The University of Akron, Akron, OH 44325, USA
2
Department of Chemical and Biomolecular Engineering, The University of Akron, Akron, OH 44325, USA
*
Author to whom correspondence should be addressed.
Received: 13 September 2018 / Revised: 9 October 2018 / Accepted: 11 October 2018 / Published: 17 October 2018
(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)
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Abstract

A combinatorial approach integrating stem cells and capable of exploiting available cues is likely needed to regenerate lost neural tissues and ultimately restore neurologic functions. This study investigates the effects of the subcutaneous maturation of adult-derived neural stem cell (aNSCs) seeded into biomaterial constructs on aNSC differentiation and ultimate regional neuronal identity as a first step toward a future spinal cord injury treatment. To achieve this, we encapsulated rat aNSCs in chitosan-based hydrogels functionalized with immobilized azide-tagged interferon-γ inside a chitosan conduit. Then, we implanted these constructs in the subcutaneous tissues in the backs of rats in the cervical, thoracic, and lumbar regions for 4, 6, and 8 weeks. After harvesting the scaffolds, we analyzed cell differentiation qualitatively using immunohistochemical analysis and quantitatively using RT-qPCR. Results revealed that the hydrogels supported aNSC survival and differentiation up to 4 weeks in the subcutaneous environment as marked by the expression of several neurogenesis markers. Most interesting, the aNSCs expressed region-specific Hox genes corresponding to their region of implantation. This study lays the groundwork for further translational work to recapitulate the potentially undiscovered patterning cues in the subcutaneous tissue and provide support for the conceptual premise that our bioengineering approach can form caudalized region-specific neuroepithelium. View Full-Text
Keywords: chitosan-based scaffold; NSCs; adult-derived neural stem cells; stem cell priming; preconditioning of neural stem cells; region-specific neural tissue; neural identity; instructive biomaterials chitosan-based scaffold; NSCs; adult-derived neural stem cells; stem cell priming; preconditioning of neural stem cells; region-specific neural tissue; neural identity; instructive biomaterials
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Farrag, M.; Leipzig, N.D. Subcutaneous Maturation of Neural Stem Cell-Loaded Hydrogels Forms Region-Specific Neuroepithelium. Cells 2018, 7, 173.

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