Human mesenchymal stromal cells small extracellular vesicles attenuate sepsis-induced acute lung injury in a mouse model: the role of oxidative stress and the mitogen-activated protein kinase/nuclear factor kappa B pathway

Chen, Jie; Li, Chonghui; Liang, Zhixin; Li, Chunsun; Li, Yanqin; Zhi-gang, Zhao; Qiu, Tian; Hao, Haojie; Niu, Ruichao; Chen, Liangan

doi:10.1016/j.jcyt.2021.05.009

Cited by 30 publications

(19 citation statements)

References 57 publications

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“…Hence, there has been a marked increase in published pre-clinical studies using MSC-EVs in animals with organ injury or immune dysfunction since 2013 until now [68]. All these studies have reinforced the crucial role of EVs derived from MSCs in reducing pathogen replication [69], phagocytosis [70], immunity regulation [71][72][73], and the regeneration of injured tissues, which are essential aspects to treat sepsis and its consequent organ dysfunction [66,67] in vitro and in vivo.…”

Section: Evs For Sepsis Treatmentmentioning

confidence: 99%

Bioengineered extracellular vesicles: future of precision medicine for sepsis

Areny-Balagueró

Solé-Porta

Camprubí-Rimblas

et al. 2023

ICMx

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Sepsis is a syndromic response to infection and is frequently a final common pathway to death from many infectious diseases worldwide. The complexity and high heterogeneity of sepsis hinder the possibility to treat all patients with the same protocol, requiring personalized management. The versatility of extracellular vesicles (EVs) and their contribution to sepsis progression bring along promises for one-to-one tailoring sepsis treatment and diagnosis. In this article, we critically review the endogenous role of EVs in sepsis progression and how current advancements have improved EVs-based therapies toward their translational future clinical application, with innovative strategies to enhance EVs effect. More complex approaches, including hybrid and fully synthetic nanocarriers that mimic EVs, are also discussed. Several pre-clinical and clinical studies are examined through the review to offer a general outlook of the current and future perspectives of EV-based sepsis diagnosis and treatment.

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Section: Evs For Sepsis Treatmentmentioning

confidence: 99%

Bioengineered extracellular vesicles: future of precision medicine for sepsis

Areny-Balagueró

Solé-Porta

Camprubí-Rimblas

et al. 2023

ICMx

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“…Liu et al transferred miR-451 into burn-induced ALI rats and found that the expressions of IL-6,TNF-α, and IL-1β along with NF-kB signaling pathway proteins were decreased; these effects were reversed when miR-451 expression was suppressed ( Liu et al, 2019 ). Chen et al injected MSC-derived exosomes into the tail veins of ALI rats and found that the MSC-derived exosomes inhibited histopathological changes and improved pulmonary microvascular permeability ( Chen et al, 2021 ). The therapeutic mechanism of these effects might be related to the inhibition of phosphorylation in the MAPK/NF-kB pathway and the degradation of IkB.…”

Section: Biological Roles Of Mscsmentioning

confidence: 99%

Advances in mesenchymal stromal cell therapy for acute lung injury/acute respiratory distress syndrome

Liu

Xiao

Xie

2022

Front. Cell Dev. Biol.

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Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) develops rapidly and has high mortality. ALI/ARDS is mainly manifested as acute or progressive hypoxic respiratory failure. At present, there is no effective clinical intervention for the treatment of ALI/ARDS. Mesenchymal stromal cells (MSCs) show promise for ALI/ARDS treatment due to their biological characteristics, easy cultivation, low immunogenicity, and abundant sources. The therapeutic mechanisms of MSCs in diseases are related to their homing capability, multidirectional differentiation, anti-inflammatory effect, paracrine signaling, macrophage polarization, the polarization of the MSCs themselves, and MSCs-derived exosomes. In this review, we discuss the pathogenesis of ALI/ARDS along with the biological characteristics and mechanisms of MSCs in the treatment of ALI/ARDS.

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“…MSC-derived EVs were shown to improve pulmonary microvascular permeability and inhibited histopathological changes and infiltration of the lung tissue with polymorphonuclear leukocytes in a CLP-sepsis model. This effect was associated with an increase in antioxidant enzymes and inhibition of NF-κB activation ( 72 ). Even macrophage polarization, an important step in the development of inflammatory lung injury, can be influenced by Exos released from bone marrow mesenchymal stem cells (BMSCs).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, different studies described the NF-κB activation as target point of MSC-derived EVs therapy. For example, miR-27b inhibited the development of sepsis by downregulating JMJD3 and inactivating the NF-κB signaling pathway ( 109 ), while the suppression of MAPK/NF-κB also inhibited pulmonary microvascular permeability, histopathological changes, and infiltration of polymorphonuclear leukocytes in septic ALI ( 72 ). In addition, functional recovery of cardiomyocytes was achieved with treatment of life-threatening complication of cardiac dysfunction with MSC-derived EVs ( 90 ).…”

Section: Introductionmentioning

confidence: 99%

The Roles of Extracellular Vesicles in Sepsis and Systemic Inflammatory Response Syndrome

Weber

Henrich

Hildebrand

et al. 2022

Shock

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Sepsis is a life-threatening organ dysfunction, caused by dysregulation of the host response to infection. To understand the underlying mechanisms of sepsis, the vast spectrum of extracellular vesicles (EVs) is gaining importance in this research field. A connection between EVs and sepsis was shown in 1998 in an endotoxemia pig model. Since then, the number of studies describing EVs as markers and mediators of sepsis increased steadily. Extracellular vesicles in sepsis could be friends and foes at the same time depending on their origin and cargo. On the one hand, transfer of EVs or outer membrane vesicles can induce sepsis or systemic inflammatory response syndrome with comparable efficiency as well-established methods, such as cecal ligation puncture or lipopolysaccharide injection. On the other hand, EVs could provide certain therapeutic effects, mediated via reduction of reactive oxygen species, inflammatory cytokines and chemokines, influence on macrophage polarization and apoptosis, as well as increase of anti-inflammatory cytokines. Moreover, EVs could be helpful in the diagnosis of sepsis. Extracellular vesicles of different cellular origin, such as leucocytes, macrophages, platelets, and granulocytes, have been suggested as potential sepsis biomarkers. They ensure the diagnosis of sepsis earlier than classical clinical inflammation markers, such as C-reactive protein, leucocytes, or IL-6. This review summarizes the three roles of EVs in sepsis-mediator/inducer, biomarker, and therapeutic tool.

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Human mesenchymal stromal cells small extracellular vesicles attenuate sepsis-induced acute lung injury in a mouse model: the role of oxidative stress and the mitogen-activated protein kinase/nuclear factor kappa B pathway

Cited by 30 publications

References 57 publications

Bioengineered extracellular vesicles: future of precision medicine for sepsis

Bioengineered extracellular vesicles: future of precision medicine for sepsis

Advances in mesenchymal stromal cell therapy for acute lung injury/acute respiratory distress syndrome

The Roles of Extracellular Vesicles in Sepsis and Systemic Inflammatory Response Syndrome

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