Autophagy-Mediated Defense Response of Mouse Mesenchymal Stromal Cells (MSCs) to Challenge with Escherichia coli

Gorbunov, Nikolai V.; Garrison, Bradley R.; Zhai, Min; McDaniel, Dennis P.; Ledney, G D; Elliott, Thomas B.; Kiang, Juliann G.

doi:10.5772/36593

Cited by 6 publications

(33 citation statements)

References 47 publications

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“…The establishment of MSC cultures used in the present research was described previously [11] when they were determined to be the bone marrow colony-forming unit fibroblasts [11, 29]. They lack hematopoietic and endothelial lineage markers (CD45, CD34, CD4, and CD117) but are positive for a wide variety of other cell surface molecules (CD44, CD105, and Sca1).…”

Section: Methodsmentioning

confidence: 99%

“…For protein analyses, MSCs were lysed and total proteins were extracted in accordance with the protocol described previously [11]. Aliquots of proteins were resolved on SDS-polyacrylamide slab gels (NuPAGE 4%–12% Bis-Tris; Invitrogen, Carlsbad, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…For expression and spatial localization of proteins in MSCs, the cells (5 specimens per group) were fixed in 2% paraformaldehyde, processed for immunestaining, and analyzed with fluorescence confocal microscopy [11]. Normal donkey serum and antibody were diluted in phosphate-buffered saline (PBS) containing 0.5% BSA and 0.15% glycine.…”

Section: Methodsmentioning

confidence: 99%

“…Blocks were processed as described previously [11]. The sections of embedded specimens were analyzed with a Philips CM100 electron microscope.…”

Section: Methodsmentioning

confidence: 99%

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Adaptive Redox Response of Mesenchymal Stromal Cells to Stimulation with Lipopolysaccharide Inflammagen: Mechanisms of Remodeling of Tissue Barriers in Sepsis

Gorbunov

Garrison

McDaniel

et al. 2013

Oxidative Medicine and Cellular Longevity

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Acute bacterial inflammation is accompanied by excessive release of bacterial toxins and production of reactive oxygen and nitrogen species (ROS and RNS), which ultimately results in redox stress. These factors can induce damage to components of tissue barriers, including damage to ubiquitous mesenchymal stromal cells (MSCs), and thus can exacerbate the septic multiple organ dysfunctions. The mechanisms employed by MSCs in order to survive these stress conditions are still poorly understood and require clarification. In this report, we demonstrated that in vitro treatment of MSCs with lipopolysaccharide (LPS) induced inflammatory responses, which included, but not limited to, upregulation of iNOS and release of RNS and ROS. These events triggered in MSCs a cascade of responses driving adaptive remodeling and resistance to a “self-inflicted” oxidative stress. Thus, while MSCs displayed high levels of constitutively present adaptogens, for example, HSP70 and mitochondrial Sirt3, treatment with LPS induced a number of adaptive responses that included induction and nuclear translocation of redox response elements such as NFkB, TRX1, Ref1, Nrf2, FoxO3a, HO1, and activation of autophagy and mitochondrial remodeling. We propose that the above prosurvival pathways activated in MSCs in vitro could be a part of adaptive responses employed by stromal cells under septic conditions.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Blocks were processed as described previously [11]. The sections of embedded specimens were analyzed with a Philips CM100 electron microscope.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Adaptive Redox Response of Mesenchymal Stromal Cells to Stimulation with Lipopolysaccharide Inflammagen: Mechanisms of Remodeling of Tissue Barriers in Sepsis

Gorbunov

Garrison

McDaniel

et al. 2013

Oxidative Medicine and Cellular Longevity

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show abstract

“…Paneth cells produce defensins to protect against bacterial entry via the gut barrier [49,50]. However, stem cells have also been shown to inhibit bacterial entry [51]. The immunofluoresence images in Fig.…”

Section: Gamma Radiation Induced Autophagy In Mouse Ileal Cryptsmentioning

confidence: 99%

Lipid Peroxidation After Ionizing Irradiation Leads to Apoptosis and Autophagy

Kiang¹,

Fukumoto²,

Gorbunov³

2012

Lipid Peroxidation

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Mesenchymal stromal cells in the antimicrobial host response of hematopoietic stem cell recipients with graft-versus-host disease—friends or foes?

et al. 2014

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Mesenchymal stromal cells (MSCs) are multipotent cells, which exhibit broad immunosuppressive activities. Moreover, they may be administered irrespectively of human leukocyte antigen (HLA) compatibility, without inducing life-threatening immunological reactions, as they express no HLA class II and limited HLA class I antigens under resting conditions. These characteristics have made MSC an appealing candidate for cell therapy after hematopoietic stem cell transplantation (HSCT), for example, for treatment of graft-versus-host disease (GvHD) or for graft rejection prevention/treatment in allogeneic HSCT recipients. Unfortunately, information regarding the effect of MSC infusion on the host response to infectious agents is scarce, and study results on infectious complications in patients receiving MSC are conflicting. The present review focuses on the available data from in vitro studies and animal models regarding the interaction of MSC with bacterial, viral and fungal pathogens. In a clinical part, we present the current information on infectious complications in allogeneic HSCT recipients who had received MSCs as prophylaxis or treatment of GvHD disease.

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Autophagy-Mediated Defense Response of Mouse Mesenchymal Stromal Cells (MSCs) to Challenge with Escherichia coli

Cited by 6 publications

References 47 publications

Adaptive Redox Response of Mesenchymal Stromal Cells to Stimulation with Lipopolysaccharide Inflammagen: Mechanisms of Remodeling of Tissue Barriers in Sepsis

Adaptive Redox Response of Mesenchymal Stromal Cells to Stimulation with Lipopolysaccharide Inflammagen: Mechanisms of Remodeling of Tissue Barriers in Sepsis

Lipid Peroxidation After Ionizing Irradiation Leads to Apoptosis and Autophagy

Mesenchymal stromal cells in the antimicrobial host response of hematopoietic stem cell recipients with graft-versus-host disease—friends or foes?

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