PMID- 37234959 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230528 IS - 1687-966X (Print) IS - 1687-9678 (Electronic) VI - 2023 DP - 2023 TI - Spermidine Retarded the Senescence of Multipotent Mesenchymal Stromal Cells In Vitro and In Vivo through SIRT3-Mediated Antioxidation. PG - 9672658 LID - 10.1155/2023/9672658 [doi] LID - 9672658 AB - Multipotent mesenchymal stromal cells (MSCs) expand in vitro and undergo replicative senescence, thereby restricting their clinical utilization. Thus, an effective strategy is required to impede MSC senescence. Since spermidine (SPD) supplementation can prolong the lifespan of yeast by inhibiting oxidative stress, spermidine is a potential option for delaying MSC senescence. In this study, to test our hypothesis, we first isolated primary human umbilical cord mesenchymal stem cells (hUCMSCs). Subsequently, the appropriate SPD dose was administered during continuous cell cultivation. Next, we evaluated the antisenescence effects by SA-beta-gal staining, Ki67 expression, reactive oxygen species (ROS) levels, adipogenic or osteogenic ability, senescence-associated markers, and DNA damage markers. The results revealed that early SPD intervention significantly delays the replicative senescence of hUCMSCs and constrains premature H(2)O(2)-induced senescence. Additionally, by silencing SIRT3, the SPD-mediated antisenescence effects disappear, further demonstrating that SIRT3 is necessary for SPD to exert its antisenescence effects on hUCMSCs. Besides, the findings of this study also suggest that SPD in vivo protects MSCs against oxidative stress and delays cell senescence. Thus, MSCs maintain the ability to proliferate and differentiate efficiently in vitro and in vivo, which reflects the potential clinical utilization of MSCs in the future. CI - Copyright (c) 2023 Hua Huang et al. FAU - Huang, Hua AU - Huang H AUID- ORCID: 0000-0002-7042-1658 AD - Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China. AD - The Center of Reproductive Medicine, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China. FAU - Zhang, Wen AU - Zhang W AD - Department of General Medicine, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China. FAU - Su, Junjie AU - Su J AD - Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China. FAU - Zhou, Bisheng AU - Zhou B AD - Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China. FAU - Han, Qingjiang AU - Han Q AD - Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China. LA - eng PT - Journal Article DEP - 20230517 PL - United States TA - Stem Cells Int JT - Stem cells international JID - 101535822 PMC - PMC10208764 COIS- The authors declare that they have no competing interests. EDAT- 2023/05/26 19:15 MHDA- 2023/05/26 19:16 PMCR- 2023/05/17 CRDT- 2023/05/26 12:20 PHST- 2022/10/05 00:00 [received] PHST- 2023/04/18 00:00 [revised] PHST- 2023/04/29 00:00 [accepted] PHST- 2023/05/26 19:16 [medline] PHST- 2023/05/26 19:15 [pubmed] PHST- 2023/05/26 12:20 [entrez] PHST- 2023/05/17 00:00 [pmc-release] AID - 10.1155/2023/9672658 [doi] PST - epublish SO - Stem Cells Int. 2023 May 17;2023:9672658. doi: 10.1155/2023/9672658. eCollection 2023.