IL-1β primed mesenchymal stromal cells moderate hemorrhagic shock-induced organ injuries

Aussel, Claude; Baudry, Nathalie; Grosbot, Marion; Caron, Cécile; Vicaut, Éric; Banzet, Sébastien; Peltzer, Juliette

doi:10.1186/s13287-021-02505-4

Cited by 14 publications

(6 citation statements)

References 58 publications

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“…The few studies using MSCs in THS showed that their administration early after hemorrhagic +/− traumatic shock limited vascular permeability by preserving the barrier junction proteins (VE-cadherin, claudin-1, and occludin-1), inhibiting the expressions of leukocyte adhesion molecules (VCAM-1 and ICAM-1) on endothelial cells, and decreasing both serum concentrations of inflammatory molecules and CD68- and MPO-positive cell tissue infiltration ( 17 ). We recently showed that IL-1β-primed MSCs attenuated hemorrhagic shock-induced early hepatic and kidney injury and dysfunction and reduced the SIRS/CARS syndrome, as shown by the decreases in the plasma cytokine concentrations and the phenotypic activation of circulating CD11bc + cells ( 242 ). MSCs would also prevent the decrease in hematopoietic progenitors induced by THS in the bone marrow ( 15 , 17 , 243 ).…”

Section: Msc-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applicationsmentioning

confidence: 99%

Therapeutic Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Prevention of Organ Injuries Induced by Traumatic Hemorrhagic Shock

et al. 2021

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Severe trauma is the principal cause of death among young people worldwide. Hemorrhagic shock is the leading cause of death after severe trauma. Traumatic hemorrhagic shock (THS) is a complex phenomenon associating an absolute hypovolemia secondary to a sudden and significant extravascular blood loss, tissue injury, and, eventually, hypoxemia. These phenomena are responsible of secondary injuries such as coagulopathy, endotheliopathy, microcirculation failure, inflammation, and immune activation. Collectively, these dysfunctions lead to secondary organ failures and multi-organ failure (MOF). The development of MOF after severe trauma is one of the leading causes of morbidity and mortality, where immunological dysfunction plays a central role. Damage-associated molecular patterns induce an early and exaggerated activation of innate immunity and a suppression of adaptive immunity. Severe complications are associated with a prolonged and dysregulated immune–inflammatory state. The current challenge in the management of THS patients is preventing organ injury, which currently has no etiological treatment available. Modulating the immune response is a potential therapeutic strategy for preventing the complications of THS. Mesenchymal stromal cells (MSCs) are multipotent cells found in a large number of adult tissues and used in clinical practice as therapeutic agents for immunomodulation and tissue repair. There is growing evidence that their efficiency is mainly attributed to the secretion of a wide range of bioactive molecules and extracellular vesicles (EVs). Indeed, different experimental studies revealed that MSC-derived EVs (MSC-EVs) could modulate local and systemic deleterious immune response. Therefore, these new cell-free therapeutic products, easily stored and available immediately, represent a tremendous opportunity in the emergency context of shock. In this review, the pathophysiological environment of THS and, in particular, the crosstalk between the immune system and organ function are described. The potential therapeutic benefits of MSCs or their EVs in treating THS are discussed based on the current knowledge. Understanding the key mechanisms of immune deregulation leading to organ damage is a crucial element in order to optimize the preparation of EVs and potentiate their therapeutic effect.

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Section: Msc-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applicationsmentioning

confidence: 99%

Therapeutic Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Prevention of Organ Injuries Induced by Traumatic Hemorrhagic Shock

et al. 2021

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“…On one hand, MSCs can improve the microenvironment via the direct effect of cytokines, chemokines, extracellular vesicles, and exosomes [ 37 ]. Our previous study has shown that proper pretreatment enhanced the therapeutic effect of MSCs by regulating anti-inflammatory agents in the exosome [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis

Pan

Wang

et al. 2022

Cell Death Dis

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The therapeutic effect of mesenchymal stem cells (MSCs) on sepsis has been well-known. However, a comprehensive understanding of the relationship between MSCs and macrophages remains elusive. Superparamagnetic iron oxide (SPIO) is one of the most commonly used tracers for MSCs. Our previous study has shown that SPIO enhanced the therapeutic effect of MSCs in a macrophage-dependent manner. However, the fate of SPIO-labeled MSCs (MSCSPIO) after infusion remains unknown and the direct interaction between MSCSPIO and macrophages remains unclear. Mice were injected intravenously with MSCSPIO at 2 h after Escherichia coli infection and sacrificed at different times to investigate their distribution and therapeutic effect. We found that MSCSPIO homed to lungs rapidly after infusion and then trapped in livers for more than 10 days. Only a few MSCSPIO homed to the spleen and there was no MSCSPIO detectable in the brain, heart, kidney, colon, and uterus. MSCSPIO tended to stay longer in injured organs compared with healthy organs and played a long-term protective role in sepsis. The mRNA expression profiles between MSCs and MSCSPIO were rather different, genes related to lipid metabolism, inflammation, and oxidative stress were changed. The levels of ROS and lipid peroxide were elevated in MSCSPIO, which confirmed that SPIO-induced ferroptosis in MSCSPIO. Ferroptosis of MSCSPIO induced by SPIO enhanced the efferocytosis of macrophages and thus enhanced the protective effect on septic mice, while the benefits were impaired after MSCSPIO were treated with Ferrostatin-1 (Fer-1) or Liproxtatin-1 (Lip-1), the inhibitors of ferroptosis. SPIO-induced ferroptosis in MSCs contributes to better therapeutic effects in sepsis by enhancing the efferocytosis of macrophages. Our data showed the efficacy and advantage of MSCSPIO as a therapeutic tool and the cell states exert different curative effects on sepsis.

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“…In several in vitro and in vivo studies, IL-1β priming maximized the immunomodulation effect of MSCs by regulating IL-6 and IL-8 expression and influencing the polarization of peritoneal macrophages ( 65 , 66 ). Moreover, systemic cytokines (IL-1α, IL-6, and IL-10) and the programmed cell death receptor (PD)-1/PD-L1 axis were decreased by IL-1β-primed MSCs on monocytes and granulocytes in HS-induced kidney and liver injury model ( 53 ). Similarly, the IL-6 concentration also decreased with adipose-derived stem cell treatment in HS-induced liver injury ( 54 ).…”

Section: New Insights Into Hs Therapeutics With Innate Immune Regulationmentioning

confidence: 99%

Innate immunity and immunotherapy for hemorrhagic shock

Huang

Gao²,

Yao

et al. 2022

Front. Immunol.

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Hemorrhagic shock (HS) is a shock result of hypovolemic injury, in which the innate immune response plays a central role in the pathophysiology ofthe severe complications and organ injury in surviving patients. During the development of HS, innate immunity acts as the first line of defense, mediating a rapid response to pathogens or danger signals through pattern recognition receptors. The early and exaggerated activation of innate immunity, which is widespread in patients with HS, results in systemic inflammation, cytokine storm, and excessive activation of complement factors and innate immune cells, comprised of type II innate lymphoid cells, CD4+ T cells, natural killer cells, eosinophils, basophils, macrophages, neutrophils, and dendritic cells. Recently, compelling evidence focusing on the innate immune regulation in preclinical and clinical studies promises new treatment avenues to reverse or minimize HS-induced tissue injury, organ dysfunction, and ultimately mortality. In this review, we first discuss the innate immune response involved in HS injury, and then systematically detail the cutting-edge therapeutic strategies in the past decade regarding the innate immune regulation in this field; these strategies include the use of mesenchymal stem cells, exosomes, genetic approaches, antibody therapy, small molecule inhibitors, natural medicine, mesenteric lymph drainage, vagus nerve stimulation, hormones, glycoproteins, and others. We also reviewed the available clinical studies on immune regulation for treating HS and assessed the potential of immune regulation concerning a translation from basic research to clinical practice. Combining therapeutic strategies with an improved understanding of how the innate immune system responds to HS could help to identify and develop targeted therapeutic modalities that mitigate severe organ dysfunction, improve patient outcomes, and reduce mortality due to HS injury.

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IL-1β primed mesenchymal stromal cells moderate hemorrhagic shock-induced organ injuries

Cited by 14 publications

References 58 publications

Therapeutic Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Prevention of Organ Injuries Induced by Traumatic Hemorrhagic Shock

Therapeutic Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Prevention of Organ Injuries Induced by Traumatic Hemorrhagic Shock

Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis

Innate immunity and immunotherapy for hemorrhagic shock

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