Prof. Dr. Hubert Löwenheim
Medizinische Universtät Tübingen, Hals-, Nasen- und Ohrenheilkunde
Mechanism of regeneration in the inner ear: new aspects
Lost sensory hair cells of the adult mammalian auditory epithelium are not replaced, resulting in permanent hearing loss. Therapeutic approaches to the treatment of hearing loss by regenerative medicine have emerged from research into clinic recent years. Drug therapies are currently about to enter clinical trials. Promising strategies for the regeneration of hair cells in the inner can be classified as gene therapy, molecular therapy and stem cell therapy.
Gene delivery systems utilizing adeno-virus vectors were used following gene deletion in mouse models, to replace mutations and improve hearing function. Hearing was rescued in mice by gene delivery using a transuterine into the otocyst in the embryo. Atho-1 delivery, also using adeno-virus vectors, was applied to recover function of hair cells treated with ototoxic aminoglycosides.
Stem cell therapy is a possible technology for the treatment of deafness. The placement of exogenous stem cell in the scala tympani or scala media of the cochlea, Rosenthal’s canal where the cochlear neurons are is possible via injection.
Human stem cells, either from native inner ear tissue, or pluripotent cells (embryonic or induced) can provide a source for cochlear cells which are a valuable model to study ototoxicity, otoprotection or otoregeneration. Varying culture conditions and testing markers for hair and supporting cell–like cells, allow for the generation of “Mini-Ears”. These “Mini-Ears” can be used as a platform technology to induce regeneration of hair cells by dedifferentiation or reprogramming strategies. Also, these models can be incorporated into drug discovery programs to enable the identification of new and better drugs to treat hearing loss.