<i>SIRT3</i> Transfection of Aged Human Bone Marrow-Derived Mesenchymal Stem Cells Improves Cell Therapy-Mediated Myocardial Repair

Zhang, Dongyang; Gao, Tong; Xu, Rongjian; Sun, Lu; Zhang, Chunfeng; Bai, Long; Chen, Wei; Liu, Kaiyu; Zhou, Yang; Jiao, Xuan; Zhang, Gui-Huan; Guo, R. S.; Li, Jing-Xuan; Gao, Ying; Jiao, Wenjie; Tian, Hao

doi:10.1089/rej.2019.2260

Cited by 23 publications

(14 citation statements)

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“…SIRT3 is associated with mitochondrial biogenesis and regulates the acetylation levels of metabolic enzymes in the mitochondria ( 34 , 35 ). SIRT3 has been demonstrated to increase the expression of CAT and SOD via the upregulation of forkhead box O3a in the nucleus ( 36 , 37 ). The excessive production of ROS can induce p53-mediated apoptosis ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

Metformin attenuates H₂O₂‑induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

et al. 2021

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Osteoporosis is a common metabolic disease that has a high incidence in postmenopausal women. Studies have indicated that oxidative damage plays an important role in the development of postmenopausal osteoporosis. Metformin has been showed to have the ability to relieve excessive oxidation. The aim of the present was to determine the therapeutic effect and potential mechanism of metformin in postmenopausal osteoporosis. Oxidative damage was stimulated in vitro by the addition of H 2 O 2 to MC3T3-E1 cells and a mouse menopausal model was also constructed. Cell viability and flow cytometry experiments were performed to determine the effects of H 2 O 2 and metformin treatment on apoptosis. Mitochondrial membrane potential was tested by JC-1 assays. Western blotting was used to detect the expression of mitochondrial apoptosis markers and antioxidant enzymes. Small interfering RNA was used to knockdown sirtuin3 (SIRT3), which was verified at the mRNA and protein levels. Bilateral ovariectomy was used to prepare menopausal mice, which were analyzed using micro-computed tomography. The results indicated that metformin is able to repair mitochondrial damage and inhibit the apoptosis of osteoblasts induced by H 2 O 2 , and also reverse bone mass loss in ovariectomized mice. Western blotting results demonstrated the involvement of SIRT3 in the production of antioxidant enzymes that are essential in protecting against mitochondrial injury. In addition, experiments with SIRT3 knockdown indicated that metformin reverses H 2 O 2 -induced osteoblast apoptosis by upregulating the expression of SIRT3 via the PI3K/AKT pathway. The results of the present reveal the pathogenesis of oxidative damage and the therapeutic effect of metformin in postmenopausal osteoporosis. They also suggest that SIRT3 is a potential drug target in the treatment of osteoporosis, with metformin being a candidate drug for modification and/or clinical application.

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Section: Discussionmentioning

confidence: 99%

Metformin attenuates H₂O₂‑induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

et al. 2021

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“…Blocking factors that negatively affect lifespan is a reasonable strategy to prevent early disability and prolong the active life of older people. Among such strategies, tested in the clinical practice or which will be translated to the clinical practice, one can highlight overcoming the insulin resistance by diet restriction [ 8 ], increasing FGF21 in blood circulation, pharmacological treatment of insulin resistance (e.g., with dehydroepiandrosterone and metformin) [ 12 , 14 ], stimulation of tissue repair by GH, oxytocin, GDF11 and TIMP2 [ 203 ], vascular regeneration with bFGF, EGF, VEGF, PDGF-AB, and BMP9, preventing the development of “inflammaging” by administering anti-inflammatory molecules, including COX-2 inhibitors, leukotriene receptor antagonists, TIMP2, or other matrix metalloproteinase inhibitors [ 210 , 263 ], overcoming the cell senescence by administration of TM5441 analogs, optimizing the autophagy and mitophagy with mTOR inhibitors (rapamycin analogs) [ 264 ], with TGF-β inhibitors [ 110 , 264 ], antioxidant therapy [ 265 , 266 ], reduction of NAD+ exhaustion [ 73 ]. The indicators and mechanisms discussed above reflect the natural and pathological aging processes.…”

Section: Discussionmentioning

confidence: 99%

Can Blood-Circulating Factors Unveil and Delay Your Biological Aging?

et al. 2020

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According to the World Health Organization, the population of over 60 will double in the next 30 years in the developed countries, which will enforce a further raise of the retirement age and increase the burden on the healthcare system. Therefore, there is an acute issue of maintaining health and prolonging active working longevity, as well as implementation of early monitoring and prevention of premature aging and age-related disorders to avoid early disability. Traditional indicators of biological age are not always informative and often require extensive and expensive analysis. The study of blood factors is a simple and easily accessible way to assess individual health and supplement the traditional indicators of a person’s biological age with new objective criteria. With age, the processes of growth and development, tissue regeneration and repair decline; they are gradually replaced by enhanced catabolism, inflammatory cell activity, and insulin resistance. The number of senescent cells supporting the inflammatory loop rises; cellular clearance by autophagy and mitophagy slows down, resulting in mitochondrial and cellular damage and dysfunction. Monitoring of circulated blood factors not only reflects these processes, but also allows suggesting medical intervention to prevent or decelerate the development of age-related diseases. We review the age-related blood factors discussed in recent publications, as well as approaches to slowing aging for healthy and active longevity.

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“…The ratio of transfection reagents to plasmid was 2 μl:1 μg. Western blot analysis was used to assess ODC protein levels as is previously reported ( 14 ). After 72 h culture, Transfected cells with GFP expression were visualized with fluorescence microscope (Leica, Germany).which was used to identify transfected cells and non-transfected cells.…”

Section: Methodsmentioning

confidence: 99%

Human Decidual Mesenchymal Stem Cells Obtained From Early Pregnancy Improve Cardiac Revascularization Postinfarction by Activating Ornithine Metabolism

Chen

Bai

et al. 2022

Front. Cardiovasc. Med.

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BackgroundCompared with bone marrow mesenchymal stem cells (BMSCs), decidual mesenchymal stem cells (DMSCs) are easy to obtain and exhibit excellent angiogenic effects, but their role in cell transplantation after myocardial infarction (MI) remains unclear.MethodsBMSCs and DMSCs were harvested from healthy donors. The effects of both cell types on angiogenesis were observed in vitro. Metabonomics analysis was performed to compare different metabolites and screen critical metabolic pathways. A murine model of acute myocardial infarction (AMI) was established, which was randomized into five groups (control, BMSC, DMSC, DMSC + ODCshRNA and BMSC + ODC consisting of 50 animals, equally divided into each group). The therapeutic effect of DMSCs on MI in rats was assessed based on neovascularization and cardiac remodeling.ResultsDMSCs exhibited a better angiogenic effect on human umbilical vein endothelial cells (HUVECs) than BMSCs in vitro. In addition, ornithine metabolism, which is associated with vascularization, was significantly increased in DMSCs. The transplantation of DMSCs in the rat MI model significantly enhanced angiogenesis of the infarct border area and improved cardiac remodeling and dysfunction postinfarction compared with BMSCs. Furthermore, inhibition of ornithine metabolism by silencing ornithine decarboxylase (ODC) in DMSCs partly abolished the benefits of DMSC transplantation.ConclusionCompared with BMSCs, DMSCs exhibited better efficacy in improving revascularization and heart remodeling post-MI via the activation of ODC-associated ornithine metabolism.

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SIRT3 Transfection of Aged Human Bone Marrow-Derived Mesenchymal Stem Cells Improves Cell Therapy-Mediated Myocardial Repair

Cited by 23 publications

References 35 publications

Metformin attenuates H₂O₂‑induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

Metformin attenuates H₂O₂‑induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

Can Blood-Circulating Factors Unveil and Delay Your Biological Aging?

Human Decidual Mesenchymal Stem Cells Obtained From Early Pregnancy Improve Cardiac Revascularization Postinfarction by Activating Ornithine Metabolism

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SIRT3 Transfection of Aged Human Bone Marrow-Derived Mesenchymal Stem Cells Improves Cell Therapy-Mediated Myocardial Repair

Cited by 23 publications

References 35 publications

Metformin attenuates H2O2‑induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

Metformin attenuates H2O2‑induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

Can Blood-Circulating Factors Unveil and Delay Your Biological Aging?

Human Decidual Mesenchymal Stem Cells Obtained From Early Pregnancy Improve Cardiac Revascularization Postinfarction by Activating Ornithine Metabolism

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Metformin attenuates H₂O₂‑induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

Metformin attenuates H₂O₂‑induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway