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

Min-Chih Li,Ruey-Hwang Chou,Frank Lin,Kuang-Hsi Chang,Chien-Yu Kao,Stella Tsai,Hung-Ching Lin,Chie-Pein Chen,Kuender Yang,Yi-Chao Hsu,Ching-Chang Cheng

doi:10.3390/ijms22136664

Abstract

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.

Highlights

Mesenchymal stromal cells (MSCs) have been demonstrated to rescue cell apoptosis and repair injury in different tissues
This study demonstrates the protective effects of Umbilical cord-derived mesenchymal stromal cells (UCMSCs) exosomes on cisplatininduced hearing loss in mice
We previously reported that UCMSC exosomes could ameliorate traumatic neuropathic pain though their anti-inflammatory effects by reducing

Summary

Introduction

Mesenchymal stromal cells (MSCs) have been demonstrated to rescue cell apoptosis and repair injury in different tissues. They can be derived from different tissues, such as bone marrow [1,2], skin tissue [3,4], adipose tissue [5], placenta [6,7], and umbilical cord (UC) [8]. Adipose tissue-derived MSCs can help in hearing repair through the secretion of factors or exosomes (paracrine effects) [12]. UCMSCs have been demonstrated to rescue cell apoptosis and repair tissue damage in different disease conditions, such as severe traumatic brain injury [8] and ischemic brain injury [13], mainly through the secretion of extracellular vesicles (EVs) [14]. UCMSC exosomes [14,16] have been demonstrated to be effective for treating inflammatory diseases [17,18,19], ischemia–reperfusion injury [20], and neurodegenerative diseases [21]

Methods

Discussion

Conclusion