International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Nervonic Acid Inhibits Replicative Senescence of Human Wharton's Jelly-Derived Mesenchymal Stem Cells

  • Sun Jeong Kim (Cell and Gene Therapy Institute, ENCell Co. Ltd.) ;
  • Soojin Kwon (Cell and Gene Therapy Institute, ENCell Co. Ltd.) ;
  • Soobeen Chung (Cell and Gene Therapy Institute, ENCell Co. Ltd.) ;
  • Eun Joo Lee (Cell and Gene Therapy Institute, ENCell Co. Ltd.) ;
  • Sang Eon Park (Cell and Gene Therapy Institute, ENCell Co. Ltd.) ;
  • Suk-Joo Choi (Department of Obstetrics and Gynecology, Samsung Medical Center) ;
  • Soo-Young Oh (Department of Obstetrics and Gynecology, Samsung Medical Center) ;
  • Gyu Ha Ryu (Department of Medical Device Management and Research, SAIHST, Sungkyunkwan University) ;
  • Hong Bae Jeon (Cell and Gene Therapy Institute, ENCell Co. Ltd.) ;
  • Jong Wook Chang (Cell and Gene Therapy Institute, ENCell Co. Ltd.)
  • Received : 2023.06.28
  • Accepted : 2023.08.01
  • Published : 2024.02.28
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Abstract

Cellular senescence causes cell cycle arrest and promotes permanent cessation of proliferation. Since the senescence of mesenchymal stem cells (MSCs) reduces proliferation and multipotency and increases immunogenicity, aged MSCs are not suitable for cell therapy. Therefore, it is important to inhibit cellular senescence in MSCs. It has recently been reported that metabolites can control aging diseases. Therefore, we aimed to identify novel metabolites that regulate the replicative senescence in MSCs. Using a fecal metabolites library, we identified nervonic acid (NA) as a candidate metabolite for replicative senescence regulation. In replicative senescent MSCs, NA reduced senescence-associated 𝛽-galactosidase positive cells, the expression of senescence-related genes, as well as increased stemness and adipogenesis. Moreover, in non-senescent MSCs, NA treatment delayed senescence caused by sequential subculture and promoted proliferation. We confirmed, for the first time, that NA delayed and inhibited cellular senescence. Considering optimal concentration, duration, and timing of drug treatment, NA is a novel potential metabolite that can be used in the development of technologies that regulate cellular senescence.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2021R1F1A1064060) and supported by the Korean Fund for Regenerative Medicine funded by the Ministry of Science and ICT, and Ministry of Health and Welfare (RS-2022-00060268). This research was also supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (RS-2023-00223069) and supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HR22C1363). This work was partly supported by the Collabo R&D between Industry, Academy, and Research Institute of MSS (S3098634), and by Samsung Medical Center (SMO1230051).

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