Molecular Therapy: Nucleic Acids (Dec 2024)
AAV-regulated Serpine2 overexpression promotes hair cell regeneration
- Qiuhan Sun,
- Fangzhi Tan,
- Xinlin Wang,
- Xingliang Gu,
- Xin Chen,
- Yicheng Lu,
- Nianci Li,
- Xiaoyun Qian,
- Yinyi Zhou,
- Ziyu Zhang,
- Man Wang,
- Liyan Zhang,
- Busheng Tong,
- Jieyu Qi,
- Renjie Chai
Affiliations
- Qiuhan Sun
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
- Fangzhi Tan
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China
- Xinlin Wang
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
- Xingliang Gu
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
- Xin Chen
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China
- Yicheng Lu
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
- Nianci Li
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
- Xiaoyun Qian
- Department of Otolaryngology-Head and Neck Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing 210008, China
- Yinyi Zhou
- Department of Neurology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
- Ziyu Zhang
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
- Man Wang
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
- Liyan Zhang
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China; Corresponding author: Liyan Zhang, State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China
- Busheng Tong
- Department of Otolaryngology, Head and Neck Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Corresponding author: Busheng Tong, Department of Otolaryngology, Head and Neck Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
- Jieyu Qi
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Department of Neurology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing 100081, China; Advanced Technology Research Institute, Beijing Institute of Technology, Jinan 250300, China; Corresponding author: Jieyu Qi, Department of Neurology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
- Renjie Chai
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China; Department of Neurology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing 100081, China; Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Southeast University Shenzhen Research Institute, Shenzhen 518063, China; Corresponding author: Renjie Chai, State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China
- Journal volume & issue
-
Vol. 35,
no. 4
p. 102396
Abstract
Inner ear hair cell (HC) damage is irreversible in mammals, but it has been shown that supporting cells (SCs) have the potential to differentiate into HCs. Serpine2, a serine protease inhibitor, encodes protease nexin 1, and this has been suggested to be a factor that promotes HC regeneration. In this study, we overexpressed Serpine2 in inner ear SCs cultured in two- and three-dimensional systems using the adeno-associated virus-inner ear (AAV-ie) vector, which promoted organoid expansion and HC differentiation. Overexpression of Serpine2 in the mouse cochlea through the round window membrane (RWM) injection promoted SC proliferation and HC regeneration, and the regenerated HCs were found to be derived from Lgr5+ SCs. Regenerated HCs have electrophysiological properties that are similar to those of native HCs. Notably, Serpine2 overexpression promoted HC survival and restored hearing of neomycin-damaged mice. In conclusion, our findings indicate that Serpine2 overexpression promotes HC regeneration and suggests that the utilization of inner ear progenitor cells in combination with AAVs might be a promising therapeutic target for hearing restoration.
