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Nervonic Acid Inhibits Replicative Senescence of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells
International Journal of Stem Cells
Published online October 12, 2023;  
© 2023 Korean Society for Stem Cell Research.

Sun Jeong Kim1,2,*, Soojin Kwon1,2,*, Soobeen Chung1,2,*, Eun Joo Lee1,2, Sang Eon Park1,2, Suk-Joo Choi3, Soo-Young Oh3, Gyu Ha Ryu4,5, Hong Bae Jeon1, Jong Wook Chang1,2,6

1Cell and Gene Therapy Institute, ENCell Co. Ltd., Seoul, Korea
2Cell and Gene Therapy Institute, Samsung Medical Center, Seoul, Korea
3Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, Korea
4Department of Medical Device Management and Research, SAIHST, Sungkyunkwan University, Seoul, Korea
5The Office of R&D Strategy & Planning, Samsung Medical Center, Seoul, Korea
6Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea
Correspondence to: Jong Wook Chang
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 115 Irwon-ro, Gangnam-gu, Seoul 06355, Korea
E-mail: jongwook.chang@samsung.com
Co-Correspondence to Hong Bae Jeon
Cell and Gene Therapy Institute, ENCell Co. Ltd., 701 Yeongdongdaero, Gangnam-gu, Seoul 06072, Korea
E-mail: jhb@encellinc.com
*These authors contributed equally to this work.
Received June 28, 2023; Revised August 1, 2023; Accepted August 1, 2023.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 : Nervonic acid, Replicative senescence, Metabolites, Mesenchymal stem cells


November 2023, 16 (4)
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