Protective mechanisms of melatonin against hydrogen-peroxide-induced toxicity in human bone-marrow-derived mesenchymal stem cells

2017 ◽  
Vol 95 (7) ◽  
pp. 773-786 ◽  
Author(s):  
Saeed Mehrzadi ◽  
Majid Safa ◽  
Seyed Kamran Kamrava ◽  
Radbod Darabi ◽  
Parisa Hayat ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
Caspase 3 ◽  
Ros Generation ◽  
Protective Agent ◽  
Antioxidant Power

Many obstacles compromise the efficacy of bone marrow mesenchymal stem cells (BM-MSCs) by inducing apoptosis in the grafted BM-MSCs. The current study investigates the effect of melatonin on important mediators involved in survival of BM-MSCs in hydrogen peroxide (H2O2) apoptosis model. In brief, BM-MSCs were isolated, treated with melatonin, and then exposed to H2O2. Their viability was assessed by MTT assay and apoptotic fractions were evaluated through Annexin V, Hoechst staining, and ADP/ATP ratio. Oxidative stress biomarkers including ROS, total antioxidant power (TAP), superoxide dismutase (SOD) and catalase (CAT) activity, glutathione (GSH), thiol molecules, and lipid peroxidation (LPO) levels were determined. Secretion of inflammatory cytokines (TNF-α and IL-6) were measured by ELISA assay. The protein expression of caspase-3, Bax, and Bcl-2, was also evaluated by Western blotting. Melatonin pretreatment significantly increased viability and decreased apoptotic fraction of H2O2-exposed BM-MSCs. Melatonin also decreased ROS generation, as well as increasing the activity of SOD and CAT enzymes and GSH content. Secretion of inflammatory cytokines in H2O2-exposed cells was also reduced by melatonin. Expression of caspase-3 and Bax proteins in H2O2-exposed cells was diminished by melatonin pretreatment. The findings suggest that melatonin may be an effective protective agent against H2O2-induced oxidative stress and apoptosis in MSC.

Osteoprotegerin Protects H2O2-Induced Bone Marrow Mesenchymal Stem Cells Damage

2019 ◽  
Vol 9 (8) ◽  
pp. 1154-1159
Author(s):  
Leitao Qi ◽  
Hongqing An
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Caspase 3 ◽  
Adipogenic Differentiation ◽  
Control Group ◽  
Stress Model ◽  
Sod Activity ◽  
Marrow Mesenchymal Stem Cells

Oxidative stress causes damage and apoptosis of bone marrow mesenchymal stem cells (BMSCs). Osteoprotegerin (OPG) regulates bone differentiation. However, whether OPG plays a role in osteogenic/adipogenic differentiation under oxidative stress remains poorly understood. Rat BMSCs were randomly divided into control group; H2O2 group, in which H2O2 was used to prepare oxidative stress model; OPG group, in which 5 μM OPG was added to BMSCs based on oxidative stress model followed by analysis of BMSCs proliferation by MTT assay, BMSCs apoptosis, expression of RUNX2, OPN, FABP4 and PPARγ2 by real time PCR, OPG and RANKL protein expression by Western blot as well as SOD activity and ROS content by spectrophotometry. Compared with control group, H2O2 significantly decreased BMSCs proliferation, increased Caspase 3 activity, downregulated RUNX2 and OPN, upregulated FABP4 and PPARγ2, decreased SOD activity and increased ROS content (P < 0.05). Under H2O2 treatment, OPG addition significantly promoted BMSCs proliferation, decreased Caspase 3 activity, increased RUNX2 and OPN expression, decreased FABP4 and PPARγ2 expression, increased SOD activity, and decreased ROS content and RANKL expression (P < 0.05). OPG can promote osteogenic differentiation of BMSCs under oxidative stress, inhibit adipogenic differentiation, and protect BMSCs from damage and promote BMSCs proliferation by regulating OPG/RANKL signaling pathway.

scholarly journals Lipocalin 2 decreases senescence of bone marrow-derived mesenchymal stem cells under sub-lethal doses of oxidative stress

2014 ◽  
Vol 19 (5) ◽  
pp. 685-693 ◽  
Author(s):  
Bahareh Bahmani ◽  
Mehryar Habibi Roudkenar ◽  
Raheleh Halabian ◽  
Ali Jahanian-Najafabadi ◽  
Fatemeh Amiri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Lipocalin 2 ◽  
Lethal Doses

scholarly journals Biocompatibility of Bone Marrow-Derived Mesenchymal Stem Cells in the Rat Inner Ear following Trans-Tympanic Administration

2020 ◽  
Vol 9 (6) ◽  
pp. 1711 ◽  
Author(s):  
Adrien A. Eshraghi ◽  
Emre Ocak ◽  
Angela Zhu ◽  
Jeenu Mittal ◽  
Camron Davies ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Inner Ear ◽  
Cell Damage ◽  
Tunel Staining ◽  
Tnf Α ◽  
Rat Cochlea ◽  
Necrosis Factor

Recent advancements in stem cell therapy have led to an increased interest within the auditory community in exploring the potential of mesenchymal stem cells (MSCs) in the treatment of inner ear disorders. However, the biocompatibility of MSCs with the inner ear, especially when delivered non-surgically and in the immunocompetent cochlea, is not completely understood. In this study, we determined the effect of intratympanic administration of rodent bone marrow MSCs (BM-MSCs) on the inner ear in an immunocompetent rat model. The administration of MSCs did not lead to the generation of any oxidative stress in the rat inner ear. There was no significant production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-12, due to BM-MSCs administration into the rat cochlea. BM-MSCs do not activate caspase 3 pathway, which plays a central role in sensory cell damage. Additionally, transferase dUTP nick end labeling (TUNEL) staining determined that there was no significant cell death associated with the administration of BM-MSCs. The results of the present study suggest that trans-tympanic administration of BM-MSCs does not result in oxidative stress or inflammatory response in the immunocompetent rat cochlea.

HIGH GLUCOSE INDUCED BONE LOSS VIA ATTENUATING THE PROLIFERATION AND OSTEOBLASTOGENESIS AND ENHANCING ADIPOGENESIS OF BONE MARROW MESENCHYMAL STEM CELLS

2013 ◽  
Vol 25 (05) ◽  
pp. 1340010 ◽  
Author(s):  
Wen-Tyng Li ◽  
Wen-Kai Hu ◽  
Feng-Ming Ho
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Loss ◽  
High Glucose ◽  
Chromatin Condensation ◽  
Diabetic Rats ◽  
Peroxisome Proliferator ◽  
Bone Marrow Mscs

Diabetes mellitus (DM) is associated with bone loss and leads to osteopenia and osteoporosis. This study was undertaken to investigate whether the impaired functions of mesenchymal stem cells (MSCs) derived from bone marrow play a role in pathogenesis of DM-associated bone loss. Bone marrow MSCs were taken from the alloxan-induced diabetic rats and normal rats. Bone mineral densities of tibias and femurs in diabetic rats decreased compared to those of normal rats as shown by dual energy X-ray absorptiometry. MSCs from diabetic rats exhibited reduced colony formation activity. The in vitro effects of high glucose (HG) (20 or 33 mM) on the growth, oxidative stress, apoptosis, and differentiation MSCs were next assessed. The viability and proliferation of MSCs derived from diabetic rats decreased significantly compared with that from normal rats. HG further suppressed the proliferation and viability of MSCs from both diabetic and normal rats. HG was associated with 38–40% increase in reactive oxygen species level and had significantly downregulated the activities of superoxide dismutase (SOD) and catalase (CAT) which could be recovered by the addition of L-ascorbic acid. The phenomena of apoptosis such as chromatin condensation and DNA fragmentation were found in cells cultured under HG conditions. As compared with 5.5 mM glucose, exposure of MSCs to HG enhanced adipogenic induction of triacylglycerol accumulation and inhibited osteogenic induction of alkaline phosphatase activity. HG increased peroxisome proliferator-activated receptor gamma expression during adipogenesis and reduced RUNX2 expression during osteoblastogenesis. These results indicate that MSCs derived from diabetic rats exhibited the inhibitory effects on cell growth and osteogenic ability. The oxidative stress, apoptosis, and adipogenic capability of MSCs were increased by HG. Furthermore, it is suggested that HG induces bone loss via attenuating the proliferation and osteoblastogenesis and enhancing adipogenesis mediated by the oxidative stress in rat bone marrow MSCs.

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