Human mesenchymal stem cells improve rat islet functionality under cytokine stress with combined upregulation of heme oxygenase-1 and ferritin

Camille, Laporte; Tubbs, Emily; Cristante, Justine; Gauchez, Anne-Sophie; Pesenti, Sandra; Lamarche, Frédéric; Cottet‐Rousselle, Cécile; Garrel, Catherine; Moisan, Anaïck; Moulis, Jean‐Marc; Fontaine, Éric; Benhamou, Pierre‐Yves; Lablanche, Sandrine

doi:10.1186/s13287-019-1190-4

Cited by 26 publications

(19 citation statements)

References 55 publications

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“…These studies suggest that MSCs enhance SOD activity in cells exposed to oxidative stimuli. Likewise, MSC‐CM increases SOD1 expression in islet cells exposed to pro‐inflammatory cytokines and SOD2 in tert‐Butyl hydroperoxide‐treated umbilical endothelial cells 77,78 . In endothelial cells, increased SOD2 expression was regulated by signal transducer and activator of transcription (STAT3) signaling and knockdown of either SOD2 or STAT3 decreased the antiapoptotic effects of the MSC‐CM 77 .…”

Section: Antioxidative Mechanisms Of Mscsmentioning

confidence: 98%

“…Glutathione reductase and GSTs are secreted by MSCs via exosomes 31 . While GSH has been the best studied scavenger in MSC treatments, they have also been demonstrated to upregulate the expression of the enzyme NAD(P)H quinone oxidoreductase 1 (NQO1) which detoxify quinones that contribute to the generation of ROS in septic lung injury, small bowel I/R injury in vivo, and cytokine‐exposed islet cell in vitro 78,84,92 …”

Section: Antioxidative Mechanisms Of Mscsmentioning

confidence: 99%

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The emerging antioxidant paradigm of mesenchymal stem cell therapy

Stavely

Nurgali

2020

Stem Cells Translational Medicine

146

101

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Mesenchymal stem cells (multipotent stromal cells; MSCs) have been under investigation for the treatment of diverse diseases, with many promising outcomes achieved in animal models and clinical trials. The biological activity of MSC therapies has not been fully resolved which is critical to rationalizing their use and developing strategies to enhance treatment efficacy. Different paradigms have been constructed to explain their mechanism of action, including tissue regeneration, trophic/anti‐inflammatory secretion, and immunomodulation. MSCs rarely engraft and differentiate into other cell types after in vivo administration. Furthermore, it is equivocal whether MSCs function via the secretion of many peptide/protein ligands as their therapeutic properties are observed across xenogeneic barriers, which is suggestive of mechanisms involving mediators conserved between species. Oxidative stress is concomitant with cellular injury, inflammation, and dysregulated metabolism which are involved in many pathologies. Growing evidence supports that MSCs exert antioxidant properties in a variety of animal models of disease, which may explain their cytoprotective and anti‐inflammatory properties. In this review, evidence of the antioxidant effects of MSCs in in vivo and in vitro models is explored and potential mechanisms of these effects are discussed. These include direct scavenging of free radicals, promoting endogenous antioxidant defenses, immunomodulation via reactive oxygen species suppression, altering mitochondrial bioenergetics, and donating functional mitochondria to damaged cells. Modulation of the redox environment and oxidative stress by MSCs can mediate their anti‐inflammatory and cytoprotective properties and may offer an explanation to the diversity in disease models treatable by MSCs and how these mechanisms may be conserved between species.

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Section: Antioxidative Mechanisms Of Mscsmentioning

confidence: 98%

Section: Antioxidative Mechanisms Of Mscsmentioning

confidence: 99%

The emerging antioxidant paradigm of mesenchymal stem cell therapy

Stavely

Nurgali

2020

Stem Cells Translational Medicine

146

101

View full text Add to dashboard Cite

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“…Understanding how MSCs exert these direct effects on islet cells may allow us to develop in vitro pretreatment protocols which replicate some of the beneficial effects of MSCs in cell‐free systems. In studies using rodent or human islets exposed to cocktails of pro‐inflammatory cytokines, MSC coculture was reported to preserve GSIS, 40,41 protect against cytokine‐induced apoptosis, and maintain islet morphology 41 . Human islets cultured in MSC‐conditioned medium were protected from apoptosis following cytokine exposure, and maintained normal islet morphology 42 .…”

Section: Mscs Protect Islets From Transplantation‐associated Cell Strmentioning

confidence: 99%

Protecting islet functional viability using mesenchymal stromal cells

Hubber

Rackham

Jones

2021

Stem Cells Translational Medicine

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Islet transplantation is an emerging treatment for type 1 diabetes which offers the prospect of physiological control of blood glucose and reductions in acute hypoglycaemic episodes. However, current protocols are limited by a rapid decline in islet functional viability during the isolation process, culture period, and post‐transplantation. Much of this can be attributed to the deleterious effects of hypoxic and cytokine stressors on β cells. One experimental strategy to improve the functional viability of islets is coculture or cotransplantation with mesenchymal stromal cells (MSCs). Numerous studies have shown that MSCs have the capacity to improve islet survival and insulin secretory function, and the mechanisms of these effects are becoming increasingly well understood. In this review, we will focus on recent studies demonstrating the capacity for MSCs to protect islets from hypoxia‐ and cytokine‐induced stress. Islets exposed to acute hypoxia (1%‐2% O2) or to inflammatory cytokines (including IFN‐γ, TNF‐α, and IL‐B) in vitro undergo apoptosis and a rapid decline in glucose‐stimulated insulin secretion. Coculture of islets with MSCs, or with MSC‐conditioned medium, protects from these deleterious effects, primarily with secreted factors. These protective effects are distinct from the immunomodulatory and structural support MSCs provide when cotransplanted with islets. Recent studies suggest that MSCs may support secretory function by the physical transfer of functional mitochondria, particularly to metabolically compromised β cells. Understanding how MSCs respond to stressed islets will facilitate the development of MSC secretome based, cell‐free approaches to supporting islet graft function during transplantation by protecting or repairing β cells.

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“…1). HO-1 by-products seem to display anti-inflammatory, antioxidant and antiapoptotic actions [44,45].…”

Section: Immunomodulatory Properties Of Mscsmentioning

confidence: 99%

Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19

Rocha

Oliveira

Noronha

et al. 2020

Stem Cell Rev and Rep

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Mesenchymal stromal cells (MSCs) constitute a heterogeneous population of stromal cells with immunomodulatory and regenerative properties that support their therapeutic use. MSCs isolated from many tissue sources replicate vigorously in vitro and maintain their main biological properties allowing their widespread clinical application. To date, most MSC-based preclinical and clinical trials targeted immune-mediated and inflammatory diseases. Nevertheless, MSCs have antiviral properties and have been used in the treatment of various viral infections in the last years. Here, we revised in detail the biological properties of MSCs and their preclinical and clinical applications in viral diseases, including the disease caused by the severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) infection (COVID-19). Notably, rapidly increasing numbers of MSC-based therapies for COVID-19 have recently been reported. MSCs are theoretically capable of reducing inflammation and promote lung regeneration in severe COVID-19 patients. We critically discuss the rationale, advantages and disadvantages of MSC-based therapies for viral infections and also specifically for COVID-19 and point out some directions in this field. Finally, we argue that MSC-based therapy may be a promising therapeutic strategy for severe COVID-19 and other emergent respiratory tract viral infections, beyond the viral infection diseases in which MSCs have already been clinically applied.

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Human mesenchymal stem cells improve rat islet functionality under cytokine stress with combined upregulation of heme oxygenase-1 and ferritin

Cited by 26 publications

References 55 publications

The emerging antioxidant paradigm of mesenchymal stem cell therapy

The emerging antioxidant paradigm of mesenchymal stem cell therapy

Protecting islet functional viability using mesenchymal stromal cells

Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19

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