Characterization of different immune suppression approaches for intracochlear transplantation of human induced pluripotent stem-cell derived otic progenitor cells in the Mongolian gerbil

Patients suffering from a denervated cochlea – loss of sensory hair cells and spiral ganglion neurons – do not profit from an electrical Cochlea implant (CI). Therefore, the focus of our research is to treat the denervated cochlea with a combination of optogenetic and regenerative methods. Previous experiments characterized the regenerative potential of human optogenetically modified otic progenitor cells (OPCs) via insertion in the denervated cochlea in a preclinical rodent model (Mongolian gerbil). It is known that treatment with ouabain – performed to reduce type I spiral ganglion cells in the modiolus – induces a strong intracochlear immune response that poses a risk for transplantation of OPCs into the cochlear modiolus. Furthermore, the surgical intracochlear approach violates the immune-privileged integrity of the cochlear additionally enhancing immune response. Thus, a cornerstone for successful transplantation of human iPSC-derived OPCs into the gerbil cochlea is an efficient protocol to suppress the local immune response. In this study, we characterize four different approaches to periinterventional immunosuppression, focusing on the comparison between systemic and local administration of immunomodulatory agents. During and after OPC onset, gerbils were treated with either cyclosporine A 15mg/kg subcutaneously with daily injections or dexamethasone 40mg/kg weekly or a combination of subcutaneous injection of cyclosporine A and dexamethasone daily. In comparison, local immunosuppression was tested by placing a Gelitta sponge containing cyclosporine A (5mg/0.1 ml) and dexamethasone (4mg/0.5ml) in the round window niche after stem cell injection. Preliminary results indicate that systemic immunosuppression is necessary to ensure successful transplantation of OPC.

Publication History

Article published online:
24 May 2022