March 9, 2022
The Jikei University School of Medicine
Keio University School of Medicine
A research group led by Professor James Hironori Okano of the Department of Regenerative Medicine, Professor Hiroki Kojima and Assistant Professor Wataru Kurihara of the Department of Otorhinolaryngology, and Professor Fusao Kato of the Department of Neuroscience at The Jikei University School of Medicine, along with Professor Masato Fujioka, Head of the Department of Molecular Genetics at Kitasato University School of Medicine (at the time of the research: Senior Lecturer, Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine), has developed a new method for culturing inner ear organoids (artificial organs) from human iPS cells and demonstrated that it can be used to evaluate the efficacy of candidate drugs for treating drug-induced hearing loss. In this study, the team succeeded in highly efficient differentiation induction by optimizing each step for culturing inner ear tissue from human iPS cells. They also established an evaluation system as a disease model by using the cultured cochlear ganglion-like cells for the first time in the world to evaluate drug effects.
The results of this study are expected to lead to the elucidation of the pathology of hearing loss and the development of new treatments.
Sensorineural hearing loss, which accounts for the majority of hearing loss cases, is known to be caused by damage to inner ear hair cells and the cochlear nerve. However, it is difficult to collect human inner ear tissue directly from patients, which has been a major hurdle for detailed pathological analysis and the development of treatments. To address this issue, this study attempted to create and utilize human iPS cell-derived inner ear tissue in a culture dish for research.
Established a method for highly efficient culture of inner ear organoids containing cochlear ganglion-like cells and hair cell-like cells from human iPS cells.
The cultured cochlear ganglion-like cells were found to have molecular expression, electrophysiological properties, and cellular morphology very similar to those of in vivo cochlear ganglion cells.
Established an evaluation system by using human cell-derived cochlear ganglion-like cells to assess drug effects for the first time in the world.
It was found that the neurotoxic effects of cisplatin (an anticancer drug) were mitigated by the administration of a CDK2 inhibitor, suggesting a potential treatment for hearing loss caused as a side effect of cisplatin.
The results of this study were published in STEM CELLS Translational Medicine on March 7.
This research was supported by JSPS KAKENHI Grant Numbers JP20K20409 and JP21H04839, and The Jikei University School of Medicine Grant for the Promotion of Joint Research Projects.
For the full press release, please see below.