scholarly journals Murine Bone Marrow Mesenchymal Stromal Cells Respond Efficiently to Oxidative Stress Despite the Low Level of Heme Oxygenases 1 and 2

2018 ◽  
Vol 29 (2) ◽  
pp. 111-127 ◽  
Author(s):  
Witold Norbert Nowak ◽  
Hevidar Taha ◽  
Neli Kachamakova-Trojanowska ◽  
Jacek Stępniewski ◽  
Joanna Agata Markiewicz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Murine Bone Marrow ◽  
Heme Oxygenases ◽  
Low Level

Murine bone marrow mesenchymal stromal cells have reduced hematopoietic maintenance ability in sickle cell disease

Blood ◽  
2021 ◽  
Author(s):  
Alice Tang ◽  
Ana Nicolle Strat ◽  
Mahmudur Rahman ◽  
Helen Zhang ◽  
Weili Bao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Stem Cell ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Tissue Injury ◽  
Cell Disease ◽  
Hematopoietic Stem

Sickle Cell Disease (SCD) is characterized by hemolytic anemia, which can trigger oxidative stress, inflammation, and tissue injury that contributes to disease complications. Bone marrow mesenchymal stromal cells (MSCs) tightly regulate hematopoietic stem cell (HSC) homeostasis in health and disease but their functionality in SCD remains unclear. We identified for the first time murine SCD MSCs to have altered gene signatures, reduced stem cell properties, and increased oxidative stress, due in part to hemolysis. Murine SCD MSCs had lower HSC maintenance ability in vitro and in vivo as manifested by increased HSC mobilization and decreased HSC engraftment following transplant. Activation of TLR4 through p65 in MSCs further contributed to MSC dysfunction. Transfusions led to improved MSC and HSC oxidative state in SCD mice. Improving the regulation between MSCs and HSCs has vital implications for enhancing clinical HSC transplantation and gene therapy outcomes and for identification of new molecular targets for alleviating SCD complications.

Suppression of Mir-93 May Regulate Anti-Oxidant Metabolism in Mesenchymal Stromal Cells Derived From Acute Myeloid Leukemia Patients.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2354-2354
Author(s):  
Peter P. Ruvolo ◽  
Rodrigo Jacamo ◽  
Teresa McQueen ◽  
Rongqing Pan ◽  
Ismael Samudio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mass Spectrometry ◽  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Energy Regulation ◽  
Glutathione Synthesis ◽  
Chromatography Mass Spectrometry ◽  
Healthy Donors ◽  
Anti Oxidant

Abstract Abstract 2354 Though still in its infancy, increasing interest is focused on the role of metabolism in cancers and leukemias. At present, most of the studies addressing this question have centered on the malignant cells themselves and not on the cells that comprise the tumor microenvironment. The leukemia microenvironment in the bone marrow has been found to provide survival advantage to AML stem cells, and to protect against chemotherapy. The underlying mechanisms, however, are not well understood. Furthermore, it is not known how the leukemic microenvironment in AML patients differs from the hematopoietic microenvironment of healthy individuals. A better understanding of leukemia will be achieved when we determine if such differences exist and importantly, how these differences could impact the microenvironment's ability to render cells resistant to therapy and possibly also support leukemogenesis. Mesenchymal stromal cells (MSC) are a key component of the bone marrow and play a key regulatory role in the leukemic niche. We have previously shown that co-cultured MSC can alter metabolism of leukemic cell lines by a mechanism involving mitochondrial uncoupling induced by the activation of Uncoupling Protein 2, to promote the Warburg Effect (Samudio et al Cancer Research, 2008; 68: 5198–5205). However, the metabolic nature of MSC from the leukemic microenvironment has not been investigated. In the present study, analysis of 352 known metabolites was performed on MSC from normal healthy donors (N = 15) and AML-derived MSC (N = 14) using Liquid Chromatography/Mass Spectrometry (LC/MS) and Gas Chromatography/Mass Spectrometry (GC/MS) (Metabolon, Durham, NC). Results indicated that metabolites involved in signaling and anti-oxidant rather than in energy regulation showed significant differences. AML derived MSC had significantly elevated levels of both reduced and oxidized glutathione compared to healthy donor MSC. Homocysteine, 5-methyltetrahydrofolate, and opthalmate levels were higher in AML MSC which is consistent with increased glutathione synthesis. The antioxidants α- and γ-tocopherol (components of vitamin E) were also significantly increased in AML MSC. These changes in key components of cellular redox homeostasis may reflect a cellular response that leads to the upregulation of glutathione synthesis and tocopherol uptake to protect the MSC cells from a more oxidative environment. In addition to metabolic analysis, we conducted miR profiling on MSC from normal healthy donors (N = 15) and AML derived MSC (N = 28). Eighteen miRs showed significant differences in expression between the 2 groups. AML derived MSC were found to express 2.3 fold less miR-93 compared to MSC from healthy donors. Previous analysis of miRs in AML cells by our groups indicated that miR-93 levels were lower in AML blast cells compared to normal counterparts (Garzon et al Blood, 2008; 111: 3183–3189). Mir-93 is a member of the miR-106b-25 cluster that comprises a group of three miRNAs on human chromosome 7q22. A recent report by Li and colleagues (Mechanisms of Ageing and Development, 2011; 132: 75–85) demonstrated in a mouse model that the aging liver is subject to damage by oxidative stress due to increased levels of miR-93. MiR-93 targets microsomal glutathione S-transferase 1 (MGST1) and the potential increase in MGST1 and the higher abundance of gluthathione support a model in which leukemia MSC could have increased xenobiotic (chemotherapy) detoxifying capacity. Future studies will include analysis of MGST1 protein expression to determine if this enzyme is indeed elevated in AML-derived MSC. In conclusion, AML-derived MSC exhibit lower expression of miR-93 that could support production of anti-oxidant metabolites to protect the cells from oxidative stress damage in the leukemic microenvironment. Disclosures: No relevant conflicts of interest to declare.

Response of murine bone marrow-derived mesenchymal stromal cells to dry-etched porous silicon scaffolds

2011 ◽  
Vol 99A (2) ◽  
pp. 269-274 ◽  
Author(s):  
Mohamad Hajj-Hassan ◽  
Maedeh Khayyat-Kholghi ◽  
Huifen Wang ◽  
Vamsy Chodavarapu ◽  
Janet E. Henderson
Keyword(s):  
Bone Marrow ◽  
Porous Silicon ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Murine Bone Marrow

Mechanisms of action and osteogenic activity of bone marrow mesenchymal stromal cells are donor dependent

2014 ◽  
Author(s):  
Julie Leotot ◽  
Angelique Lebouvier ◽  
Philippe Hernigou ◽  
Helene Rouard ◽  
Nathalie Chevallier
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Mechanisms Of Action ◽  
Osteogenic Activity
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