Academic Journal
Glutaminase-1 inhibition alleviates senescence of Wharton’s jelly-derived mesenchymal stem cells via senolysis
| العنوان: | Glutaminase-1 inhibition alleviates senescence of Wharton’s jelly-derived mesenchymal stem cells via senolysis |
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| المؤلفون: | Lee, Eun Joo, Kim, Sun Jeong, Jeon, Su Yeon, Chung, Soobeen, Park, Sang Eon, Kim, Jae‑Sung, Choi, Suk-Joo, Oh, Soo-Young, Ryu, Gyu Ha, Jeon, Hong Bae, Chang, Jong Wook |
| المساهمون: | National Research Foundation of Korea, Korean government, Ministry of Health and Welfare |
| المصدر: | Stem Cells Translational Medicine ; ISSN 2157-6564 2157-6580 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2024 |
| الوصف: | Replicative senescence of mesenchymal stem cells (MSCs) caused by repeated cell culture undermines their potential as a cell therapy because of the reduction in their proliferation and therapeutic potential. Glutaminase-1 (GLS1) is reported to be involved in the survival of senescent cells, and inhibition of GLS1 alleviates age-related dysfunction via senescent cell removal. In the present study, we attempted to elucidate the association between MSC senescence and GLS1. We conducted in vitro and in vivo experiments to analyze the effect of GLS1 inhibition on senolysis and the therapeutic effects of MSCs. Inhibition of GLS1 in Wharton’s jelly-derived MSCs (WJ-MSCs) reduced the expression of aging-related markers, such as p16, p21, and senescence-associated secretory phenotype genes, by senolysis. Replicative senescence-alleviated WJ-MSCs, which recovered after short-term treatment with bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide 3 (BPTES), showed increased proliferation and therapeutic effects compared to those observed with senescent WJ-MSCs. Moreover, compared to senescent WJ-MSCs, replicative senescence-alleviated WJ-MSCs inhibited apoptosis in serum-starved C2C12 cells, enhanced muscle formation, and hindered apoptosis and fibrosis in mdx mice. These results imply that GLS1 inhibition can ameliorate the therapeutic effects of senescent WJ-MSCs in patients with muscle diseases such as Duchenne muscular dystrophy. In conclusion, GLS1 is a key factor in modulating the senescence mechanism of MSCs, and regulation of GLS1 may enhance the therapeutic effects of senescent MSCs, thereby increasing the success rate of clinical trials involving MSCs. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/stcltm/szae053 |
| DOI: | 10.1093/stcltm/szae053/58787897/szae053.pdf |
| الاتاحة: | http://dx.doi.org/10.1093/stcltm/szae053 https://academic.oup.com/stcltm/advance-article-pdf/doi/10.1093/stcltm/szae053/58787897/szae053.pdf |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.39818CBD |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/stcltm/szae053 |
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