Engraftment and differentiation of embryonic stem cell–derived neural progenitor cells in the cochlear nerve trunk: Growth of processes into the organ of corti
Year: 2006
Type: article
Abstract: Hearing loss in mammals is irreversible because cochlear neurons and hair cells do not regenerate. To determine whether we could replace neurons lost to primary neuronal degeneration, we injected EYFP-expressing embryonic stem cell-derived mouse neural progenitor cells into the cochlear nerve trunk in immunosuppressed animals 1 week after destroying the cochlear nerve (spiral ganglion) cells while leaving hair cells intact by ouabain application to the round window at the base of the cochlea in gerbils. At 3 days post transplantation, small grafts were seen that expressed endogenous EYFP and could be immunolabeled for neuron-specific markers. Twelve days after transplantation, the grafts had neurons that extended processes from the nerve core toward the denervated organ of Corti. By 64-98 days, the grafts had sent out abundant processes that occupied a significant portion of the space formerly occupied by the cochlear nerve. The neurites grew in fasciculating bundles projecting through Rosenthal's canal, the former site of spiral ganglion cells, into the osseous spiral lamina and ultimately into the organ of Corti, where they contacted hair cells. Neuronal counts showed a significant increase in neuronal processes near the sensory epithelium, compared to animals that were denervated without subsequent stem cell transplantation. The regeneration of these neurons shows that neurons differentiated from stem cells have the capacity to grow to a specific target in an animal model of neuronal degeneration.
Source: Journal of Neurobiology
DOI: 10.1002/neu.20310
Language: English
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: G1577052167, NATURE AND MECHANISMS OF ODORANT RECEPTOR GENE CHOICE, Inner Ear Progenitor Cells, Core Support for Hearing Research - "NIDCD" Research Core Center P30, Cellular therapy for the inner ear, Conversion of stem cells to cell types of the inner ear, Cochlear synaptopathy in noise-induced and age-related hearing loss: mechanisms and treatments
OpenAlex ID: W2020768773