PhD Ajou University School of Medicine, Republic of Korea
Abstract: Age-related hearing loss (ARHL) is a type of hearing loss that occurs gradually in many individuals as they age. Studying ARHL in clinical research is challenging due to the need for long-term studies. The auditory system is complex, consisting of hair cells, nerve cells, and various supporting cells, which makes it difficult to model ARHL accurately. ‘Organoid’ technology offers a potential solution to overcome these limitations. However, there has been no successful report of establishing a human ARHL organoid model to date. In this study, we aimed to construct an ARHL disease organoid model using microRNA (miRNA) specifically found in ARHL patients. First, we screened for miRNAs that are highly expressed in the blood of ARHL patients. Next, we cloned the target miRNA into a doxycycline-inducible vector and transduced them into induced pluripotent stem cells (iPSCs) using lentivirus. These iPSCs were then differentiated into inner ear organoids, and doxycycline was administered to induce the overexpression of the target miRNA, thereby modeling ARHL. Target miRNA-induced inner ear organoids exhibited increased expression of senescence-related genes and decreased expression of auditory hair cell-related genes compared to normal inner ear organoids. Immunohistochemistry and flow cytometry results demonstrated that target miRNA overexpression led to a decreased proportion of cells expressing auditory hair cell markers such as MYO7A, and an increased expression of aging markers like P53 and P62. These findings suggest that the induction of target miRNA could potentially create an ARHL model in inner ear organoids. This represents a significant discovery that could contribute to a better understanding of the pathogenesis of ARHL and the development of novel therapeutic strategies.
Funding Source: This research was supported by the Korean Fund for Regenerative Medicine (KFRM) grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Health & Welfare) (22A0303L1-01).
