Nanofibrous scaffolds for the guidance of stem cell-derived neurons for auditory nerve regeneration

Autor: Che Chan, Sandra Hackelberg, Christina M. White, Ryan J. Miller, Long He, Benjamin R. Loomis, Liqian Liu, Josef M. Miller, Samuel J. Tuck, Arjun Rastogi, R. Keith Duncan, Joseph M. Corey, Diane M. Prieskorn
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Cell Transplantation
Cellular differentiation
Nanofibers
lcsh:Medicine
Biocompatible Materials
Deafness
Nervous System
Nerve Fibers
Tissue engineering
Animal Cells
Medicine and Health Sciences
Nanotechnology
lcsh:Science
Neurons
Mammals
Staining
Multidisciplinary
Nerves
Cell Staining
Cell Differentiation
Animal Models
Cell biology
medicine.anatomical_structure
Experimental Organism Systems
Physical Sciences
Vertebrates
Engineering and Technology
Female
Stem cell
Cellular Types
Anatomy
Neuronal Differentiation
Research Article
Neurite
Green Fluorescent Proteins
Guinea Pigs
Materials Science
Biology
Research and Analysis Methods
Rodents
Auditory Nerves
03 medical and health sciences
Precursor cell
medicine
Neurites
otorhinolaryngologic diseases
Animals
Humans
Cochlear Nerve
Spiral ganglion
Embryonic Stem Cells
Materials by Attribute
Nanomaterials
Tissue Engineering
Regeneration (biology)
lcsh:R
Organisms
Biology and Life Sciences
Cell Biology
Neuronal Dendrites
Embryonic stem cell
Nerve Regeneration
030104 developmental biology
Specimen Preparation and Treatment
Cellular Neuroscience
Amniotes
lcsh:Q
Brain Stem
Developmental Biology
Neuroscience
Zdroj: PLoS ONE, Vol 12, Iss 7, p e0180427 (2017)
PLoS ONE
ISSN: 1932-6203
Popis: Impairment of spiral ganglion neurons (SGNs) of the auditory nerve is a major cause for hearing loss occurring independently or in addition to sensory hair cell damage. Unfortunately, mammalian SGNs lack the potential for autonomous regeneration. Stem cell based therapy is a promising approach for auditory nerve regeneration, but proper integration of exogenous cells into the auditory circuit remains a fundamental challenge. Here, we present novel nanofibrous scaffolds designed to guide the integration of human stem cell-derived neurons in the internal auditory meatus (IAM), the foramen allowing passage of the spiral ganglion to the auditory brainstem. Human embryonic stem cells (hESC) were differentiated into neural precursor cells (NPCs) and seeded onto aligned nanofiber mats. The NPCs terminally differentiated into glutamatergic neurons with high efficiency, and neurite projections aligned with nanofibers in vitro. Scaffolds were assembled by seeding GFP-labeled NPCs on nanofibers integrated in a polymer sheath. Biocompatibility and functionality of the NPC-seeded scaffolds were evaluated in vivo in deafened guinea pigs (Cavia porcellus). To this end, we established an ouabain-based deafening procedure that depleted an average 72% of SGNs from apex to base of the cochleae and caused profound hearing loss. Further, we developed a surgical procedure to implant seeded scaffolds directly into the guinea pig IAM. No evidence of an inflammatory response was observed, but post-surgery tissue repair appeared to be facilitated by infiltrating Schwann cells. While NPC survival was found to be poor, both subjects implanted with NPC-seeded and cell-free control scaffolds showed partial recovery of electrically-evoked auditory brainstem thresholds. Thus, while future studies must address cell survival, nanofibrous scaffolds pose a promising strategy for auditory nerve regeneration.
Databáze: OpenAIRE
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