Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice
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....
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| Veröffentlicht in: | International journal of molecular sciences 2021-07, Vol.22 (13), p.6664 |
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| creator | Tsai, Stella Yang, Kuender Chang, Kuang-Hsi Lin, Frank Chou, Ruey-Hwang Li, Min-Chih Cheng, Ching-Chang Kao, Chien-Yu Chen, Chie-Pein Lin, Hung-Ching Hsu, Yi-Chao |
| description | 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. |
| doi_str_mv | 10.3390/ijms22136664 |
| format | Article |
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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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22136664</identifier><identifier>PMID: 34206364</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Apoptosis ; Chemotherapy ; Cisplatin ; Cochlea ; Deafness ; Degenerative diseases ; Exosomes ; Flow cytometry ; Gene expression ; Growth factors ; Hair cells ; Hearing ; Hearing loss ; Injection ; Injury prevention ; Mesenchyme ; Ototoxicity ; Outer hair cells ; Proteins ; Regenerative medicine ; Repair ; Stromal cells ; Tissue engineering ; Traumatic brain injury ; Umbilical cord</subject><ispartof>International journal of molecular sciences, 2021-07, Vol.22 (13), p.6664</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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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.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>34206364</pmid><doi>10.3390/ijms22136664</doi><orcidid>https://orcid.org/0000-0003-2694-1207</orcidid><orcidid>https://orcid.org/0000-0001-9071-475X</orcidid><orcidid>https://orcid.org/0000-0002-4453-0068</orcidid><orcidid>https://orcid.org/0000-0001-5301-2345</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis Chemotherapy Cisplatin Cochlea Deafness Degenerative diseases Exosomes Flow cytometry Gene expression Growth factors Hair cells Hearing Hearing loss Injection Injury prevention Mesenchyme Ototoxicity Outer hair cells Proteins Regenerative medicine Repair Stromal cells Tissue engineering Traumatic brain injury Umbilical cord |
| title | Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice |
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