The Protective Effects of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in Noise-Induced Hearing Loss of Rats

So Young Kim; Jeoung Eun Lee; Sung Hun Kang; So Min Lee; Jiwon Jeon; Dong Ryul Lee

doi:10.3390/cells11213524

The Protective Effects of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in Noise-Induced Hearing Loss of Rats

Cells. 2022 Nov 7;11(21):3524. doi: 10.3390/cells11213524.

Authors

So Young Kim¹, Jeoung Eun Lee², Sung Hun Kang³, So Min Lee¹, Jiwon Jeon¹, Dong Ryul Lee^{2

4}

Affiliations

¹ Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, CHA University, Seongnam-si 13496, Korea.
² CHA Advanced Research Institute, Seongnam-si 13488, Korea.
³ School of Medicine, CHA University, Seongnam-si 13488, Korea.
⁴ Department of Biomedical Science, CHA University, Seongnam-si 13488, Korea.

Abstract

A few prior animal studies have suggested the transplantation or protective effects of mesenchymal stem cells (MSCs) in noise-induced hearing loss. This study intended to evaluate the fates of administered MSCs in the inner ears and the otoprotective effects of MSCs in the noise-induced hearing loss of rats. Human embryonic stem cell-derived MSCs (ES-MSCs) were systematically administered via the tail vein in adult rats. Eight-week-old Sprague-Dawley rats were randomly allocated to the control (n = 8), ES-MSC (n = 4), noise (n = 8), and ES-MSC+noise (n = 10) groups. In ES-MSC and ES-MSC+noise rats, 5 × 10⁵ ES-MSCs were injected via the tail vein. In noise and ES-MSC+noise rats, broadband noise with 115 dB SPL was exposed for 3 h daily for 5 days. The hearing levels were measured using auditory brainstem response (ABR) at 4, 8, 16, and 32 kHz. Cochlear histology was examined using H&E staining and cochlear whole mount immunofluorescence. The presence of human DNA was examined using Sry PCR, and the presence of human cytoplasmic protein was examined using STEM121 immunofluorescence staining. The protein expression levels of heat shock protein 70 (HSP70), apoptosis-inducing factor (AIF), poly (ADP-ribose) (PAR), PAR polymerase (PARP), caspase 3, and cleaved caspase 3 were estimated. The ES-MSC rats did not show changes in ABR thresholds following the administration of ES-MSCs. The ES-MSC+ noise rats demonstrated lower ABR thresholds at 4, 8, and 16 kHz than the noise rats. Cochlear spiral ganglial cells and outer hair cells were more preserved in the ES-MSC+ noise rats than in the noise rats. The Sry PCR bands were highly detected in lung tissue and less in cochlear tissue of ES-MSC+noise rats. Only a few STEM121-positivities were observed in the spiral ganglial cell area of ES-MSC and ES-MSC+noise rats. The protein levels of AIF, PAR, PARP, caspase 3, and cleaved caspase 3 were lower in the ES-MSC+noise rats than in the noise rats. The systemic injection of ES-MSCs preserved hearing levels and attenuated parthanatos and apoptosis in rats with noise-induced hearing loss. In addition, a tiny number of transplanted ES-MSCs were observed in the spiral ganglial areas.

Keywords: cochlea; hearing loss; mesenchymal stem cells; noise; stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Auditory Threshold / physiology
Caspase 3
Hearing Loss, Noise-Induced* / pathology
Human Embryonic Stem Cells* / metabolism
Humans
Mesenchymal Stem Cells* / metabolism
Poly(ADP-ribose) Polymerase Inhibitors
Rats
Rats, Sprague-Dawley

Substances

Caspase 3
Poly(ADP-ribose) Polymerase Inhibitors

Grants and funding

This research was supported by funding from the National Research Foundation (NRF) of Korea (NRF-2019R1A6A1A03032888 and 2020R1A2C4002594) and a grant from the Research Driven Hospital R&D project, funded by the CHA Bundang Medical Center (grant number: BDCHA R&D 2021-003). The funders had no role in the design of the study, the collection, analysis and interpretation of the data or the writing of the manuscript.