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Controlling differentiation and proliferation in human stem cells intended for therapeutic use.Our ability to hear depends on auditory sensory hair cells and their associated neurons that reside in the cochlea.
OTOSTEM plans to develop two strategies using human stem cells for curing hearing loss: 1) stem cell-derived cellular agents for cell-based therapy and 2) stem cell-derived assays as a screening tool to identify novel drugs. In WP5, in vivo hearing loss models will be used to investigate efficacy of cell- and drug-based therapies. For cell transplantation purposes, enriched otic progenitors will be differentiated along sensory vs.
The main objective of WP1 is to provide a solid foundation for the whole project by defining the core cell type of the assay, the purified otic progenitor cell. OTOSTEM has identified the principal technological hurdles for the development of cell-based and drug-based hearing loss therapies and addresses these hurdles in successive and systematic manner. We approach this using several different methods and allow our visitors the broadest information of stem cell treatment available on the globe. Treatment is available now and can be searched by selecting a condition from the drop down box above. The exquisite sensitivity of the inner ear comes with the risk for damage for example by noise trauma, ototoxic drug damage, infections, age-related degeneration and genetic causes.
To be safe and effective for therapy, transplantable human otic stem cells must be reliably produced in both purity and quantity.


The four different rodent species employed are ideal in vivo models for a wide range of human hearing conditions. This technology is unprecedented in the field of translational hearing research and provides a solid platform for screening efforts and for further validation in vitro and in vivo (WP5). This will be based on functional and differentiation abilities, at the single cell transcriptional level and other important cell biological parameters such as surface markers and proliferative potential.
Otic progenitor populations in high purity will be differentiated into cochlear cell types such as sensory cells, supporting cells and neurons.
Once lost, the sensory hair cells are never replaced resulting in chronic hearing impairment. At the etiological level the main causes of hearing loss including infection, drug induced ototoxicity, noise induced trauma, and age related degeneration are addressed. In WP4, we will design bioassays capable of identifying (a) otoprotective compounds that will prevent death of human hair cells, and otoregenerative compounds that stimulate hair cell regeneration.
Recent zebrafish-based screening efforts demonstrated that 21 FDA-approved drugs out of 1,040 well- known bioactive compounds (NINDS Custom Collection II) display selective toxicity to lateral line sensory hair cells.
Teratoma formation capacity of enriched otic progenitors versus the non-enriched heterogeneous population will be investigated by injection into severe combined immunodeficient (SCID) mice.The endpoint of WP2 is to provide enriched and proven non-tumorigenic otic progenitor cells with the capacity to potentially restore the hearing function by cell transplantation in in vivo animal models (WP5). The results are reliable cell-based assays using bankable progenitor cells that are generated with highly reproducible techniques. The intended cross validation from different stem cell sources (hESCs, hiPSCs, native human fetal and adult inner ear stem cells) represents a unique opportunity and particular strength of the OTOSTEM consortium that will provide an unprecedented potential for optimization and selection of the most suitable human stem cell protocols to generate otic progenitors and differentiated cells.
Hearing impairment is a devastating and highly prevalent disorder with widespread implications for the individual and society as a whole.


Likewise, identification of drug candidates requires extensive in vitro and in vivo investigations.
At the cellular level the loss of sensory hair cells as well as auditory neurons is targeted. It is presumed that many drugs that are currently in use or in various stages of clinical trials have ototoxic potential. Adult onset hearing loss alone ranks among the five leading causes of burden of disease in Europe entailing enormous socio-economic costs.
OTOSTEM intends to bring new therapies to the point of entering a pre-clinical developmental stage in order to prepare grounds for clinical development.
Ototoxicity tests with human hESCs and hiPSCs derived inner ear cells will be established with aminoglycosides and cisplatin – known ototoxic drugs that cause hearing loss and are in widespread clinical use. Prosthetic treatment with hearing aids and cochlear implants is limited in restoring normal hearing, and reaches only every fifth patient. Hearing aid amplification or cochlear implant stimulation often fail to improve language comprehension and hence perform unsatisfactory. OTOSTEM addresses this urgent and unmet medical need for causal hearing loss therapies by focusing on human stem cell technology.



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