Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Genome Edited Sirt1-Overexpressing Human Mesenchymal Stem Cells Exhibit Therapeutic Effects in Treating Collagen-Induced Arthritis

  • Chae, Dong-Sik (Department of Orthopedic Surgery, International St. Mary's Hospital, Catholic Kwandong University College of Medicine) ;
  • Han, Seongho (Department of Family Medicine, Dong-A University Medical Center, Dong-A University College of Medicine) ;
  • Lee, Min-Kyung (Department of Dental Hygine, Dong-Eui Universtigy) ;
  • Kim, Sung-Whan (Department Medicine, Catholic Kwandong University College of Medicine)
  • Received : 2021.02.16
  • Accepted : 2021.04.01
  • Published : 2021.04.30
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Abstract

Even though mesenchymal stem cells (MSCs) are known for cartilage regeneration, their therapeutic efficacy needs to be enhanced. In the present study, we produced genome-edited silent information regulator 2 type 1 (Sirt1)-overexpressing MSCs, and evaluated their therapeutic potential in a damaged cartilage mouse liver fibrosis model. The Sirt1 gene was successfully inserted into a 'safe harbor' genomic locus in amniotic mesenchymal stem cells (AMMs), and the chondrogenic properties of the Sirt1 gene overexpressing AMMs (AMM/S) were characterized using quantitative PCR and histology. Therapeutic potentials were investigated in a collagen-induced arthritis (CIA) mouse model. Chondrocyte-differentiated AMM/S expressed cartilage-specific genes and were positive for Safranin O staining. Transplantation of AMM/S attenuated CIA progression and suppressed T helper (Th)-17 cell activation while increasing the Treg cell population in CIA mice. Pro-inflammatory factors, such as interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α were significantly decreased in AMM/S-injected joint tissues. In conclusion, genome-edited AMM/S may represent a safe and alternative therapeutic option for the treatment and repair of damaged cartilage, or in inflammatory joint arthritis.

Keywords

Acknowledgement

This work was financially supported through National Research Foundation (NRF) of Korea grants funded by the Korean Government (No. NRF-2016R1A2B4012683) and the research fund of Catholic Kwandong University for Dr. S.-W. Kim; the research fund of Dong-A University for Dr. S. Han; and an NRF of Korea grant funded by the Korean government (No. NRF-2020R1C1C101316611) for Dr. D.-S. Chae.

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