Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice

International Journal of Molecular Sciences

Hung-Ching Lin¹  Chie-Pein Chen²  Kuender D. Yang²  Kuang-Hsi Chang³  Stella Chin-Shaw Tsai⁴  Frank Cheau-Feng Lin⁵  Ruey-Hwang Chou⁶  Yi-Chao Hsu⁷  Min-Chih Li⁷  Ching-Chang Cheng⁸  Chien-Yu Kao⁹ 

[1] Department of Audiology and Speech-Language Pathology, Mackay Medical College, New Taipei City 252, Taiwan;Department of Medical Research, Mackay Memorial Hospital, Taipei 104, Taiwan;Department of Medical Research, Tungs’ Taichung Metroharbor Hospital, Taichung 435, Taiwan;Department of Otolaryngology, Tungs’ Taichung Metroharbor Hospital, Taichung 435, Taiwan;Department of Thoracic Surgery, Chung Shan Medical University Hospital, Taichung 402, Taiwan;Graduate Institute of Biomedical Sciences, China Medical University, Taichung 406, Taiwan;Institute of Biomedical Sciences, Mackay Medical College, New Taipei City 252, Taiwan;Laboratory Animal Service Center, Office of Research and Development, China Medical University, Taichung 406, Taiwan;Medical and Pharmaceutical Industry Technology and Development Center, New Taipei City 248, Taiwan;

关键词: mesenchymal stromal cells;    cisplatin;    hair cells;    inner ear;    ototoxicity;    extracellular vesicles;   

DOI  :  10.3390/ijms22136664

来源: DOAJ

【 摘 要 】

Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 μg/μL) injection at the same time point; and (ii) UCMSC exosome (1.2 μg/μL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin-injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity-induced hearing loss by promoting tissue remodeling and repair.

【 授权许可】

Unknown