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Research Paper|Volume 14, Issue 5|pp 2194—2209

Tonsil mesenchymal stem cells-derived extracellular vesicles prevent submandibular gland dysfunction in ovariectomized rats

Ji Min Kim1, Jeong Hun Kim2, Keunyoung Kim3, Sung-Chan Shin4, Yong-Il Cheon4, Hyung Sik Kim5,6, Jin-Choon Lee7, Eui-Suk Sung7, Minhyung Lee7, Gi-Cheol Park8, Byung-Joo Lee2,4
  • 1Pusan National University Medical Research Institute, Pusan National University School of Medicine, Pusan National University, Busan, Republic of Korea
  • 2Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
  • 3Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
  • 4Department of Otorhinolaryngology-Head and Neck Surgery, Pusan National University School of Medicine, Pusan National University, Busan, Republic of Korea
  • 5Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
  • 6Institute for Translational Dental Science, Pusan National University, Yangsan, Republic of Korea
  • 7Department of Otorhinolaryngology-Head and Neck Surgery, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam, Republic of Korea
  • 8Department of Otolaryngology-Head and Neck Surgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea
Received: October 1, 2021Accepted: February 11, 2022Published: March 13, 2022
https://doi.org/10.18632/aging.203947

Copyright: © 2022 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Dry mouth that occurs after menopause significantly reduces the quality of life of the elderly. The extracellular vesicles derived from mesenchymal stem cells are being studied for application in various pathological conditions in the field of tissue regenerative medicine. This study is to investigate the therapeutic effect on salivary gland dysfunction occurring after ovariectomy using tonsil mesenchymal stem cells (T-MSCs)-derived extracellular vesicles. The rats were divided into the following groups: sham-operated rats (SHAM), rats that underwent ovariectomy (OVX), and rats that underwent OVX surgery and were simultaneously injected with T-MSC-derived extracellular vesicles (OVX+EV). The rats were sacrificed 6 weeks after ovariectomy. Estradiol levels decreased in the OVX group compared with those in the SHAM group. Extracellular vesicles had no effect on estradiol levels or estrogen receptor β expression. The evaluation of pro-inflammatory cytokines, TNF-α and IL-6, increased in the OVX group and decreased in the OVX+EV group. The expressions of collagen I and TGFβI increased in the OVX group but decreased in the OVX+EV group. Moreover, to examine submandibular gland function, AQP5 and α-amylase expressions were downregulated in the OVX group, but improved upon exosome injection. In conclusion, T-MSC-derived extracellular vesicles are useful for the prevented submandibular gland dysfunction that occurs after menopause.