Mouse Models of Sepsis and Septic Shock

Korneev, Kirill V.

doi:10.1134/s0026893319050108

Cited by 54 publications

(47 citation statements)

References 172 publications

(235 reference statements)

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“…Furthermore, the treatment efficacy may be affected by the timing of MSC administration as some researchers failed to identify any positive effects of MSC when administered 6 h post-CLP induction while other identified positive correlation when used at 24 h pre-CLP induction and up to 24 h post-induction. Similar contradictory findings were seen in the route of administration used whereby intraperitoneal injections of MSCs were able to decrease demise of LPS-induced septic mice in one study while the same method resulted in slightly more deaths among CLP-induced septic rats in another investigation ( 68 , 70 ).…”

Section: Mscs For the Treatment Of Neonatal Sepsismentioning

confidence: 61%

“…A variety of animal sepsis models have been established depending on the use of different bacterial pathogens such as P. aeruginosa and E.coli , induction with a toxic agent such as lipopolysaccharide (LPS) as well as disruption to the tissue barrier integrity such as cecal ligation and puncture (CLP) ( 67 – 70 ). Using these animal models, the effects of a variety of MSC variables have been tested, including dosage, timing, and route of MSC administration.…”

Section: Mscs For the Treatment Of Neonatal Sepsismentioning

confidence: 99%

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The Potential of Mesenchymal Stromal Cell as Therapy in Neonatal Diseases

et al. 2020

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Mesenchymal stromal cells (MSCs) can be derived from various tissue sources, such as the bone marrow (BMSCs), adipose tissue (ADSCs), umbilical cord (UC-MSCs) and umbilical cord blood (UCB-MSCs). Clinical trials have been conducted to investigate the potential of MSCs in ameliorating neonatal diseases, including bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC). In preclinical studies, MSC therapy has been tested for the treatment of various neonatal diseases affecting the heart, eye, gut, and brain as well as sepsis. Up to date, the number of clinical trials using MSCs to treat neonatal diseases is still limited. The data reported thus far positioned MSC therapy as safe with positive outcomes. However, most of these trials are still preliminary and generally smaller in scale. Larger trials with more appropriate controls and a longer follow-up period need to be conducted to prove the safety and efficacy of the therapy more conclusively. This review discusses the current application of MSCs in treating neonatal diseases, its mechanism of action and future direction of this novel therapy, including the potential of using MSC-derived extracellular vesicles instead of the cells to treat various clinical conditions in the newborn.

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Section: Mscs For the Treatment Of Neonatal Sepsismentioning

confidence: 61%

Section: Mscs For the Treatment Of Neonatal Sepsismentioning

confidence: 99%

The Potential of Mesenchymal Stromal Cell as Therapy in Neonatal Diseases

et al. 2020

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“…Along with the rampant production of cytokines, another clinical aspect of endotoxic shock that can lead to mortality is the formation of blood clots in the smaller vessels, leading to multiorgan failure ( 16 , 17 ). To address this, we analyzed the serum of LPS i.p.-treated mice to assess differences in coagulation.…”

Section: Resultsmentioning

confidence: 99%

A conserved long noncoding RNA, GAPLINC, modulates the immune response during endotoxic shock

Vollmers

Covarrubias

Kuang

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Recent studies have identified thousands of long noncoding RNAs (lncRNAs) in mammalian genomes that regulate gene expression in different biological processes. Although lncRNAs have been identified in a variety of immune cells and implicated in immune response, the biological function and mechanism of the majority remain unexplored, especially in sepsis. Here, we identify a role for a lncRNA—gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC)—previously characterized for its role in cancer, now in the context of innate immunity, macrophages, and LPS-induced endotoxic shock. Transcriptome analysis of macrophages from humans and mice reveals that GAPLINC is a conserved lncRNA that is highly expressed following macrophage differentiation. Upon inflammatory activation, GAPLINC is rapidly down-regulated. Macrophages depleted of GAPLINC display enhanced expression of inflammatory genes at baseline, while overexpression of GAPLINC suppresses this response. Consistent with GAPLINC-depleted cells, Gaplinc knockout mice display enhanced basal levels of inflammatory genes and show resistance to LPS-induced endotoxic shock. Mechanistically, survival is linked to increased levels of nuclear NF-κB in Gaplinc knockout mice that drives basal expression of target genes typically only activated following inflammatory stimulation. We show that this activation of immune response genes prior to LPS challenge leads to decreased blood clot formation, which protects Gaplinc knockout mice from multiorgan failure and death. Together, our results identify a previously unknown function for GAPLINC as a negative regulator of inflammation and uncover a key role for this lncRNA in modulating endotoxic shock.

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“…Here, direct evidence of the involvement of lncRNAs in SICD is summarized (Figure 2). This evidence is based on the findings from basic molecular biological research using animal models of hypodynamic septic shock induced by LPS and cecal ligation and puncture (CLP) (27); cardiac muscle cell lines (primary culture cardiomyocytes, H9C2, HL-1, and AC-16 cell lines) and microvascular cell lines exposed to serum from septic patients or administered with LPS (28); and clinical studies of sepsis patients subjected to cardiac dysfunction (Table 1).…”

Section: Lncrna Involved In Sicd Among Various Cell Typesmentioning

confidence: 99%

The Role of Long Non-coding RNAs in Sepsis-Induced Cardiac Dysfunction

Zhang

et al. 2021

Front. Cardiovasc. Med.

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Sepsis is a syndrome with life-threatening organ dysfunction induced by a dysregulated host response to infection. The heart is one of the most commonly involved organs during sepsis, and cardiac dysfunction, which is usually indicative of an extremely poor clinical outcome, is a leading cause of death in septic cases. Despite substantial improvements in the understanding of the mechanisms that contribute to the origin and responses to sepsis, the prognosis of sepsis-induced cardiac dysfunction (SICD) remains poor and its molecular pathophysiological changes are not well-characterized. The recently discovered group of mediators known as long non-coding RNAs (lncRNAs) have presented novel insights and opportunities to explore the mechanisms and development of SICD and may provide new targets for diagnosis and therapeutic strategies. LncRNAs are RNA transcripts of more than 200 nucleotides with limited or no protein-coding potential. Evidence has rapidly accumulated from numerous studies on how lncRNAs function in associated regulatory circuits during SICD. This review outlines the direct evidence of the effect of lncRNAs on SICD based on clinical trials and animal studies. Furthermore, potential functional lncRNAs in SICD that have been identified in sepsis studies are summarized with a proven biological function in research on other cardiovascular diseases.

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Mouse Models of Sepsis and Septic Shock

Cited by 54 publications

References 172 publications

The Potential of Mesenchymal Stromal Cell as Therapy in Neonatal Diseases

The Potential of Mesenchymal Stromal Cell as Therapy in Neonatal Diseases

A conserved long noncoding RNA, GAPLINC, modulates the immune response during endotoxic shock

The Role of Long Non-coding RNAs in Sepsis-Induced Cardiac Dysfunction

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