scholarly journals Oxidative stress induces imbalance of adipogenic/osteoblastic lineage commitment in mesenchymal stem cells through decreasing SIRT1 functions

2017 ◽  
Author(s):  
Chia-Hua Lin ◽  
Nan-Ting Li ◽  
Hui-Shan Cheng ◽  
Men-Luh Yen
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lineage Commitment ◽  
Osteoblastic Lineage

scholarly journals THU0495 NOVEL UNDERSTANDING OF THE PATHOGENESIS OF JUVENILE IDIOPATHIC ARTHRITIS: FOCUS ON MESENCHYMAL STEM CELLS IMPAIRMENT, SENESCENCE AND IMMUNOREGULATORY FUNCTION

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 483.2-484
Author(s):  
L. Zaripova ◽  
A. Midgley ◽  
S. Christmas ◽  
E. Baildam ◽  
R. Oldershaw
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Juvenile Idiopathic Arthritis ◽  
Metabolic Activity ◽  
Healthy Controls ◽  
High Level ◽  
Pro Inflammatory Cytokines

Background:Juvenile idiopathic arthritis (JIA) is a well-known chronic rheumatic disease of childhood characterised by progressive joint destruction and severe systemic complications.Immune cells are known to trigger the pathophysiological cascade in JIA, but there is little information regarding the contribution made by Mesenchymal stem cells (MSCs). These cells are able to modulate the immune response and decrease the level of pro-inflammatory cytokines. With addition of regenerative property it makes MSCs potential candidates for clinical application as immunosuppressants in treatment of autoimmune diseases.Objectives:To investigate MSCs proliferation, viability and immunomodulatory function in JIA and healthy children.Methods:MSCs were separated from peripheral blood (PB) and synovial fluid (SF) of JIA patients and healthy controls. Cell proliferation rate was counted by Population doublings per day (PDD) during 9 days, in the last of which alamarBlue™ assays were performed to assess cell viability. Due to measure senescence MSCs were stained with SA-β-galactosidase. Immunofluorescence was used to examine the expression of p16, p21, p53. Oxidative stress was measured with DCFH-DA. Cell cycle analysis was evaluated with Propidium Iodide and analysed by Accuri® C6 Flow Cytometer.Commercially-available bone marrow mesenchymal stem cells (BM-MSCs) were treated with graded concentrations of pro-inflammatory cytokines (0.1-100 ng/ml) with following examination of cell viability. Mixed lymphocyte reactions (MLR) were performed to measure MSC immunomodulatory abilityin vitro.Results:The growth kinetics of JIA-MSCs were different from healthy controls. JIA-MSCs divided slowly and appeared disorganised with large cytoplasm and loads of outgrowth. They demonstrated a decrease in cell proliferation (negative PDD) and metabolic activity. Difference in growth kinetics and metabolic activity were found inside the JIA PB group with some evidence of response following biological treatment. Thus, PB-MSCs from patients treated with TNFi and anti-IL6 medications had notably higher cell proliferation and metabolic activity against JIA patients received other therapy. Considering this difference, it was hypothesised that cytokines obtained in a high amount in PB and SF of JIA patients may influence MSCs viability. To prove this BM-MSCs were treated with cytokines and demonstrated a dose-dependent decrease in metabolic activity significantly after TNFα and IL1, no significantly after treatment with IL6. Both BM-MSCs treated with cytokines and JIA-MSCs displayed high level of reactive oxygen species.Cell cycle analysis revealed that JIA-MSCs were arrested in G0/G1 phase with low number of mitotic cells. In addition, the number of senescence-associated SA-β-gal-positive cells was notably higher in JIA-MSCs. Furthermore, JIA-MSCs expressed high level of immunofluorescence for p16, p21 and p53 which played an important role in regulating the senescence progress of MSCs.Results of MLR showed the ability of BM-MSCs to decrease the percentage of activated T-helpers, T-suppressors, B-cells and natural killers proliferation, while JIA-MSCs lost this property.Conclusion:Taken together current research has demonstrated that under the influence of proinflammatory cytokines JIA-MSCs suffered from oxidative stress and disruption of metabolic activity acquire senescent morphology, shorten of telomere length, arrest in G0 phase of cell cycle and finally loss of immune regulation. We are continuing our research to determine the mechanisms that are responsible for the impaired phenotype with the aim of identifying new therapeutic strategies for the treatment of JIA.Disclosure of Interests: :None declared

scholarly journals Hsp20-Engineered Mesenchymal Stem Cells are Resistant to Oxidative Stress Via Enhanced Activation of Akt and Increased Secretion of Growth Factors

Stem Cells ◽  
2009 ◽  
pp. N/A-N/A ◽  
Author(s):  
Xiaohong Wang ◽  
Tiemin Zhao ◽  
Wei Huang ◽  
Tao Wang ◽  
Jiang Qian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors

In Vitro High-Capacity Assay to Quantify the Clonal Heterogeneity in Trilineage Potential of Mesenchymal Stem Cells Reveals a Complex Hierarchy of Lineage Commitment

Stem Cells ◽  
2010 ◽  
Vol 28 (4) ◽  
pp. 788-798 ◽  
Author(s):  
Katie C. Russell ◽  
Donald G. Phinney ◽  
Michelle R. Lacey ◽  
Bonnie L. Barrilleaux ◽  
Kristin E. Meyertholen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
High Capacity ◽  
Lineage Commitment ◽  
Clonal Heterogeneity

scholarly journals High Throughput Transcriptome Profiling of Lithium Stimulated Human Mesenchymal Stem Cells Reveals Priming towards Osteoblastic Lineage

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e55769 ◽  
Author(s):  
Neeraj Kumar Satija ◽  
Deepa Sharma ◽  
Farhat Afrin ◽  
Rajendra P. Tripathi ◽  
Gurudutta Gangenahalli
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
High Throughput ◽  
Human Mesenchymal Stem Cells ◽  
Transcriptome Profiling ◽  
Osteoblastic Lineage

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 Exosomes Derived from Bone Mesenchymal Stem Cells Alleviate Compression-Induced Nucleus Pulposus Cell Apoptosis by Inhibiting Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yiqiang Hu ◽  
Ranyang Tao ◽  
Linfang Wang ◽  
Lang Chen ◽  
Ze Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Nucleus Pulposus ◽  
Cell Apoptosis ◽  
Nucleus Pulposus Cell ◽  
Inhibitory Effect ◽  
Bone Mesenchymal Stem Cells ◽  
Induced Apoptosis ◽  
Ivd Degeneration

Oxidative stress is relevant in compression-induced nucleus pulposus (NP) cell apoptosis and intervertebral disc (IVD) degeneration. Exosomes derived from bone mesenchymal stem cells (BMSCs-Exos) are key secretory products of MSCs, with important roles in tissue regeneration. This research is aimed at studying the protective impact of BMSCs-Exos on NP cell apoptosis caused by compression and investigating the underlying mechanisms. Our results indicated that we isolated BMSCs successfully. Exosomes were isolated from the BMSCs and found to alleviate the inhibitory effect that compression has on proliferation and viability in NP cells, decreasing the toxic effects of compression-induced NP cells. AnnexinV/PI double staining and TUNEL assays indicated that the BMSCs-Exos reduced compression-induced apoptosis. In addition, our research found that BMSCs-Exos suppressed compression-mediated NP oxidative stress by detecting the ROS and malondialdehyde level. Furthermore, BMSCs-Exos increased the mitochondrial membrane potential and alleviated compression-induced mitochondrial damage. These results indicate that BMSCs-Exos alleviate compression-mediated NP apoptosis by suppressing oxidative stress, which may provide a promising cell-free therapy for treating IVD degeneration.

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