Application of optogenetically modified stem cells in therapy of neuropathic hearing loss

A large number of patients suffering from severe hearing impairment caused by the loss of function of spiral ganglion neurons (SGN) – cochlear neuropathy – do not profit from an electrical Cochlea implant (CI). Regeneration of lost or dysfunctional SGN using human optogenetically modified otic progenitor cells (OPCs) would open up the possibility of therapy with an optical CI for this group of patients. OPCs for the therapy of cochlear neuropathy could be obtained from otic 3D cell cultures (otic organoids), which are based on human induced pluripotent stem cells. We established a preclinical rodent model (Mongolian gerbil) for neuropathic hearing loss through application of ouabain to the round window niche and could demonstrate a significant reduction of type I SGN in the basal, mid and apical cochlear turn and a threshold shift of 40 dB after ouabain treatment. Subsequently, the thus denervated cochleae were injected with OPC, equipped with a light-gated Ion channel, directly into the cochlear modiolus. Peri- and postoperative systemic immunosuppression with dexamethasone led to successful intramodiolar cell transplantation (n = 3) demonstrated by immunohistochemical staining of cryosections of the corresponding cochleae. Further experiments investigated the functional properties of transplanted OPCs by measuring auditory evoked brainstem potentials (ABR) through optical stimulation of the cochlea.

Publication History

Article published online:
12 May 2023