Auditory Systems of the Future

Regeneration of hair cells in the inner ear by means of stem cell therapy

The diversity of cell types in the inner ear presents a great challenge in terms of therapy. Newly generated hair cells can function only if they are in their correct physiological position – in contact with the tectorial membrane and with the processes of the spiral ganglion cells. MHH’s Department of Otolaryngology is currently developing a molecular biological positioning system, which allows targeted stem cell transplantation with the aim of replacing damaged hair cells in the inner ear.

 

Regeneration of hair cells in the inner ear through genetic engineering

Certain nutrients can protect the auditory nerve cells after an incident that impaired the sense of hearing or equilibrium. Experiments have shown that these nutrients not only improve cell survival but also stimulate new cell growth. However, these nutrients have no reliable effect if absorbed in the form of pills or intravenous infusions – they must be directly applied into the inner ear using application systems, which enable long-term nutrient administration.

In cell-based methods of application, the nutrient is continuously produced and released by a specific cell over a long period of time. This is why cells are genetically modified for two reasons: to guarantee the release of nutrients into the inner ear over a long period of time, and to replace destroyed hair cells. These genetically modified cells can either be applied directly into the inner ear of a deaf individual or onto the electrode surface of hearing implants (such as cochlear implants). As soon as the electrode is inserted into the inner ear, the desired effect is achieved.

Stem cells seem particularly suited for this method. After genetic modification, they can be stimulated to either produce nutrients or to identify a previously destroyed cell type. The great advantage is that they are autologous (i. e. the patient’s own) cells, and thus rejection responses can be prevented.

Since 2015, a biological therapy has been available at MHH’s Department of Otorhinolaryngology. This involves coating the CI electrode with autologous stem cells (during cochlear implantation), to improve hearing. This new technique is unique worldwide and delivers promising results:

 

The Patient’s Own Cells Improve the Success of Cochlear Implantation

Professor Thomas Lenarz and his team of experts at MHH’s Department of Otorhinolaryngology now offer an internationally unique way to improve hearing for cochlear implant recipients. The surgeons insert a CI electrode coated with autologous (i.e. the patient’s own) stem cells – called progenitor cells – obtained from the bone marrow into the inner ear. The results of this state-of-the art therapy, which has been available for adults at MHH for around a year, are more than promising.

The principle is rather simple. During cochlear implantation, a small blood sample is taken from the patient’s bone marrow located in the breast bone, and the progenitor cells are then isolated by centrifugation in the operating theatre. These progenitors are produced directly by the stem cell and required for blood formation. They have two important functions in the inner ear. Not only do they reduce scar formation around the electrode, but they also create ideal conditions for the auditory nerve fibres to ‘flourish’, thus stimulating their growth towards the electrode. Both effects result in significantly improved signal transmission from the electrode to the auditory nerve, and therefore improved hearing.

‘We will continue to develop this therapy and are hoping to obtain approval for its use in children in a few years so that all CI recipients benefit from this approach’, confirms Professor Lenarz, the Director of the world’s leading centre for cochlear implants and implantable hearing systems. To date, around 8,000 individuals have received a CI at MHH, and every year approximately another 500 are implanted.

Professor Lenarz and Dr. Athanasia Warnecke from the Department of Otorhinolaryngology and the German Hearing Center (Deutsches HörZentrum Hannover, DHZ) at the Medical University of Hannover (Medizinische Hochschule Hannover, MHH) have already invested around five years of research and are investigating this novel approach as part of the ‘Hearing4all’ Cluster of Excellence. The aim is to make hearing with a CI as similar as possible to natural hearing. So far the system is highly conductive to speech understanding, but the sound quality in challenging acoustic situations – such as a noisy background or when listening to music – can still be improved upon. However, as the number of electrode contacts cannot be greatly increased (otherwise the electrode’s flexibility would be restricted, potentially causing damage to the delicate structures in the inner ear), researchers must find other ways to improve the transmission quality. In contrast to the inner ear with its estimated 30,000 hair cells, whose job it is to transmit the signals, a CI only possesses a maximum of 22 electrode contacts. There are several ways to combat the resulting signal compression and its negative influence on sound quality. One approach is therapy with autologous progenitor cells, the aim being to develop this until it is established as a routine clinical procedure.