Antioxidant Properties of Tonsil-Derived Mesenchymal Stem Cells on Human Vocal Fold Fibroblast Exposed to Oxidative Stress

The therapeutic potential of tonsil-derived mesenchymal stem cells (TMSCs) has been proved in several in vitro and in vivo models based on their antioxidative capacity. Oxidative stress is involved in the formation of vocal fold scars and the aging of vocal folds. However, few studies have examined...

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Main Authors: Sung-Chan Shin, Hyung-Sik Kim, Yoojin Seo, Cho Hee Kim, Ji Min Kim, Hyun-Keun Kwon, Jin-Choon Lee, Eui-Suk Sung, Byung-Joo Lee
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2020/2560828
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author Sung-Chan Shin
Hyung-Sik Kim
Yoojin Seo
Cho Hee Kim
Ji Min Kim
Hyun-Keun Kwon
Jin-Choon Lee
Eui-Suk Sung
Byung-Joo Lee
author_facet Sung-Chan Shin
Hyung-Sik Kim
Yoojin Seo
Cho Hee Kim
Ji Min Kim
Hyun-Keun Kwon
Jin-Choon Lee
Eui-Suk Sung
Byung-Joo Lee
author_sort Sung-Chan Shin
collection DOAJ
description The therapeutic potential of tonsil-derived mesenchymal stem cells (TMSCs) has been proved in several in vitro and in vivo models based on their antioxidative capacity. Oxidative stress is involved in the formation of vocal fold scars and the aging of vocal folds. However, few studies have examined the direct correlation between oxidative damage and reconstitution of extracellular matrix (ECM) in the vocal fold fibrosis. We, therefore, sought to investigate the impact of oxidative stress on cell survival and ECM production of human vocal fibroblasts (hVFFs) and the protective effects elicited by TMSCs against oxidative damages in hVFFs. hVFFs were exposed to different concentrations of tert-butyl hydroperoxide in the presence or absence of TMSCs. Cell viability and reactive oxygen species (ROS) production were assessed to examine the progression of oxidative stress in vitro. In addition, expression patterns of ECM-associated factors including various collagens were examined by real-time PCR and immunocytochemical analysis. We found that both cell viability and proliferation capacity of hVFFs were decreased following the exposure to tBHP in a dose-dependent manner. Furthermore, tBHP treatment induced the generation of ROS and reactive aldehydes, while it decreased endogenous activity of antioxidant enzymes in hVFF. Importantly, TMSCs could rescue these oxidative stress-associated damages of hVFFs. TMSCs also downregulated tBHP-mediated production of proinflammatory cytokines in hVFFs. In addition, coculture with TMSC could restore the endogenous matrix metalloproteinase (MMP) activity of hVFFs upon tBHP treatment and, in turn, reduce the oxidative stress-induced ECM accumulation in hVFFs. We have, therefore, shown that the changes in hVFF proliferative capacity and ECM gene expression induced by oxidative stress are consistent with in vivo phenotypes observed in aging vocal folds and vocal fold scarring and that TMSCs may function to reduce oxidative stress in aging vocal folds.
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spelling doaj-art-a60ef685a5444f9c91e1343067ed8cfa2025-02-03T01:00:06ZengWileyStem Cells International1687-966X1687-96782020-01-01202010.1155/2020/25608282560828Antioxidant Properties of Tonsil-Derived Mesenchymal Stem Cells on Human Vocal Fold Fibroblast Exposed to Oxidative StressSung-Chan Shin0Hyung-Sik Kim1Yoojin Seo2Cho Hee Kim3Ji Min Kim4Hyun-Keun Kwon5Jin-Choon Lee6Eui-Suk Sung7Byung-Joo Lee8Department of Otorhinolaryngology, Head and Neck Surgery, Pusan National University School of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of KoreaDepartment of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of KoreaDental and Life Science Institute, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of KoreaDepartment of Otorhinolaryngology, Head and Neck Surgery, Pusan National University School of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of KoreaDepartment of Otorhinolaryngology, Head and Neck Surgery, Pusan National University School of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of KoreaDental and Life Science Institute, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of KoreaDepartment of Otorhinolaryngology, Head and Neck Surgery, Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Yangsan Hospital, Yangsan, Gyeongsangnam-do 50612, Republic of KoreaDepartment of Otorhinolaryngology, Head and Neck Surgery, Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Yangsan Hospital, Yangsan, Gyeongsangnam-do 50612, Republic of KoreaDepartment of Otorhinolaryngology, Head and Neck Surgery, Pusan National University School of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of KoreaThe therapeutic potential of tonsil-derived mesenchymal stem cells (TMSCs) has been proved in several in vitro and in vivo models based on their antioxidative capacity. Oxidative stress is involved in the formation of vocal fold scars and the aging of vocal folds. However, few studies have examined the direct correlation between oxidative damage and reconstitution of extracellular matrix (ECM) in the vocal fold fibrosis. We, therefore, sought to investigate the impact of oxidative stress on cell survival and ECM production of human vocal fibroblasts (hVFFs) and the protective effects elicited by TMSCs against oxidative damages in hVFFs. hVFFs were exposed to different concentrations of tert-butyl hydroperoxide in the presence or absence of TMSCs. Cell viability and reactive oxygen species (ROS) production were assessed to examine the progression of oxidative stress in vitro. In addition, expression patterns of ECM-associated factors including various collagens were examined by real-time PCR and immunocytochemical analysis. We found that both cell viability and proliferation capacity of hVFFs were decreased following the exposure to tBHP in a dose-dependent manner. Furthermore, tBHP treatment induced the generation of ROS and reactive aldehydes, while it decreased endogenous activity of antioxidant enzymes in hVFF. Importantly, TMSCs could rescue these oxidative stress-associated damages of hVFFs. TMSCs also downregulated tBHP-mediated production of proinflammatory cytokines in hVFFs. In addition, coculture with TMSC could restore the endogenous matrix metalloproteinase (MMP) activity of hVFFs upon tBHP treatment and, in turn, reduce the oxidative stress-induced ECM accumulation in hVFFs. We have, therefore, shown that the changes in hVFF proliferative capacity and ECM gene expression induced by oxidative stress are consistent with in vivo phenotypes observed in aging vocal folds and vocal fold scarring and that TMSCs may function to reduce oxidative stress in aging vocal folds.http://dx.doi.org/10.1155/2020/2560828
spellingShingle Sung-Chan Shin
Hyung-Sik Kim
Yoojin Seo
Cho Hee Kim
Ji Min Kim
Hyun-Keun Kwon
Jin-Choon Lee
Eui-Suk Sung
Byung-Joo Lee
Antioxidant Properties of Tonsil-Derived Mesenchymal Stem Cells on Human Vocal Fold Fibroblast Exposed to Oxidative Stress
Stem Cells International
title Antioxidant Properties of Tonsil-Derived Mesenchymal Stem Cells on Human Vocal Fold Fibroblast Exposed to Oxidative Stress
title_full Antioxidant Properties of Tonsil-Derived Mesenchymal Stem Cells on Human Vocal Fold Fibroblast Exposed to Oxidative Stress
title_fullStr Antioxidant Properties of Tonsil-Derived Mesenchymal Stem Cells on Human Vocal Fold Fibroblast Exposed to Oxidative Stress
title_full_unstemmed Antioxidant Properties of Tonsil-Derived Mesenchymal Stem Cells on Human Vocal Fold Fibroblast Exposed to Oxidative Stress
title_short Antioxidant Properties of Tonsil-Derived Mesenchymal Stem Cells on Human Vocal Fold Fibroblast Exposed to Oxidative Stress
title_sort antioxidant properties of tonsil derived mesenchymal stem cells on human vocal fold fibroblast exposed to oxidative stress
url http://dx.doi.org/10.1155/2020/2560828
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