Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Extracellular Vesicles Derived from Adipose Stem Cells Alleviate Systemic Sclerosis by Inhibiting TGF-β Pathway

  • Eunae Kim (School of Pharmacy, Sungkyunkwan University) ;
  • Hark Kyun Kim (School of Pharmacy, Sungkyunkwan University) ;
  • Jae Hoon Sul (School of Pharmacy, Sungkyunkwan University) ;
  • Jeongmi Lee (School of Pharmacy, Sungkyunkwan University) ;
  • Seung Hyun Baek (School of Pharmacy, Sungkyunkwan University) ;
  • Yoonsuk Cho (School of Pharmacy, Sungkyunkwan University) ;
  • Jihoon Han (School of Pharmacy, Sungkyunkwan University) ;
  • Junsik Kim (School of Pharmacy, Sungkyunkwan University) ;
  • Sunyoung Park (School of Pharmacy, Sungkyunkwan University) ;
  • Jae Hyung Park (Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University) ;
  • Yong Woo Cho (ExoStemTech Inc.) ;
  • Dong-Gyu Jo (School of Pharmacy, Sungkyunkwan University)
  • Received : 2023.11.03
  • Accepted : 2023.11.30
  • Published : 2024.07.01
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Abstract

Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor β (TGF-β) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-β1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-β pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-β1. Finally, TGF-β1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea (NRF-2019R1A2C3011422, NRF-2019R1A5A2027340). This work was also supported by the Korea Drug Development Fund (KDDF-HN21C1266) and the Ministry of Oceans and Fisheries' R&D project, Korea (1525011845).

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