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An Engineered Three-Dimensional Stem Cell Niche in the Inner Ear by Applying a Nanofibrillar Cellulose Hydrogel with a Sustained-Release Neurotrophic Factor Delivery System

63 Pages Posted: 26 Nov 2019 Publication Status: Accepted

See all articles by Hsiang-Tsun Chang

Hsiang-Tsun Chang

Northwestern University - Department of Otolaryngology and Head and Neck Surgery

Andrew M. Oleksijew

Northwestern University - Department of Neurology

Kyle S. Coots

Northwestern University - Department of Communication Sciences and Disorders

Rachel A. Heuer

Northwestern University - Hugh Knowles Center for Hearing Research

Kevin T. Nella

Independent

Christian B. Roque

Independent

Tammy L. McGuire

Independent

Akihiro Joseph Matsuoka

Northwestern University - Department of Otolaryngology and Head and Neck Surgery

Abstract

Although the application of human embryonic stem cells (hESCs) in stem cell-replacement therapy remains promising, its potential is hindered by low cell survival rate in post-transplantation within the inner ear. Here, we aim to enhance the in vitro and in vivo survival rate and neuronal differentiation of otic neuronal progenitors (ONPs) by generating an artificial stem cell niche consisting of three-dimensional (3D) hESC-derived ONP spheroids with a nanofibrillar cellulose hydrogel and a sustained-release brain-derivative neurotrophic factor delivery system. Our results demonstrated that the transplanted hESC-derived ONP spheroids survived and neuronally differentiated into an otic neuronal lineage in vitro and in vivo, and extended neurites toward the bony wall of the cochlea in vivo. Our data in vitro and in vivo presented here provide sufficient evidence that we have established a robust, reproducible protocol for in vivo transplantation of hESC-derived ONPs to the inner ear. Using our protocol to create an artificial stem cell niche in the inner ear, it is now possible to work on integrating transplanted hESC-derived ONPs further and also to work toward achieving functional auditory neurons generated from hESCs. Our findings suggest that the provision of an artificial stem cell niche is a fruitful future approach to stem cell-replacement therapy for inner ear regeneration.

Keywords: human embryonic stem cells, stem cell niche, spiral ganglion neurons, the inner ear, hydrogel, human pluripotent stem cells, stem cell-replacement therapy, brain-derived neurotrophic factor

Suggested Citation

Chang, Hsiang-Tsun and Oleksijew, Andrew M. and Coots, Kyle S. and Heuer, Rachel A. and Nella, Kevin T. and Roque, Christian B. and McGuire, Tammy L. and Matsuoka, Akihiro Joseph, An Engineered Three-Dimensional Stem Cell Niche in the Inner Ear by Applying a Nanofibrillar Cellulose Hydrogel with a Sustained-Release Neurotrophic Factor Delivery System (November 20, 2019). Available at SSRN: https://ssrn.com/abstract=3490431 or http://dx.doi.org/10.2139/ssrn.3490431

Hsiang-Tsun Chang (Contact Author)

Northwestern University - Department of Otolaryngology and Head and Neck Surgery

United States

Andrew M. Oleksijew

Northwestern University - Department of Neurology

Chicago, IL
United States

Kyle S. Coots

Northwestern University - Department of Communication Sciences and Disorders

United States

Rachel A. Heuer

Northwestern University - Hugh Knowles Center for Hearing Research

United States

Kevin T. Nella

Independent

Christian B. Roque

Independent

Tammy L. McGuire

Independent

Akihiro Joseph Matsuoka

Northwestern University - Department of Otolaryngology and Head and Neck Surgery ( email )

United States

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