Engraftment and differentiation of embryonic stem cell–derived neural progenitor cells in the cochlear nerve trunk: Growth of processes into the organ of corti

TLDR

Hearing loss in mammals is irreversible because cochlear neurons and hair cells do not regenerate. The study aimed to test whether embryonic stem cell–derived neural progenitor cells could replace lost cochlear neurons after selective spiral ganglion ablation while preserving hair cells. They injected EYFP‑labeled embryonic stem cell–derived neural progenitor cells into the cochlear nerve trunk of immunosuppressed gerbils one week after ouabain‑induced spiral ganglion ablation. The transplanted progenitors survived, differentiated into neurons, and extended abundant, fasciculating processes that reached the denervated organ of Corti and contacted hair cells, resulting in a significant increase in neuronal processes near the sensory epithelium. © 2006 Wiley Periodicals, Inc.

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. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006