Antimicrobial effects of mesenchymal stem cells primed by modified LPS on bacterial clearance in sepsis

Saeedi, Pouya; Halabian, Raheleh; Fooladi, Abbas Ali Imani

doi:10.1002/jcp.27298

Cited by 44 publications

(36 citation statements)

References 35 publications

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“…This dysregulation of the immune response during sepsis results in an overreaction of the immune system to eliminate pathogens, which can be accompanied by tissue damage, organ failure, and death (Al‐Hasan & Justo, ). Infection can be attributed to many pathogens (fungi, virus, and parasite), but it is usually due to gram‐positive or gram‐negative bacteria (Saeedi, Halabian, & Fooladi, ). Sepsis is an important reason for morbidity and mortality in hospital.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effects of curcumin on sepsis and mechanisms of action: A systematic review of preclinical studies

Karimi

Ghodsi

Kooshki

et al. 2019

Phytotherapy Research

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Sepsis is a complex disease that begins with an infectious disorder and causes excessive immune responses. Curcumin is considered as an active component of turmeric that can improve the condition in sepsis due to its anti‐inflammatory and antioxidant properties. PubMed, Embase, Google Scholar, Web of Science, and Scopus databases were searched. Searching was not limited to a specific publication period. Only English‐language original articles, which had examined the effect of curcumin on sepsis, were included. At first, 1,098 articles were totally found, and 209 articles were selected after excluding duplicated data; 46 articles were remained due to the curcumin effects on sepsis. These included 23 in vitro studies and 23 animal studies. Our results showed that curcumin and various analogs of curcumin can have an inhibitory effect on sepsis‐induced complications. Curcumin has the ability to inhibit the inflammatory, oxidative coagulation factors, and regulation of immune responses in sepsis. Despite the promising evidence of the therapeutic effects of curcumin on the sepsis complication, further studies seem necessary to investigate its effect and possible mechanisms of action in human studies.

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Section: Introductionmentioning

confidence: 99%

Therapeutic effects of curcumin on sepsis and mechanisms of action: A systematic review of preclinical studies

Karimi

Ghodsi

Kooshki

et al. 2019

Phytotherapy Research

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“…Priming MSCs via exposure to bacteria, or bacteria-derived LPS, has been shown to further enhance their antibacterial properties 20,21,44 . Here, C57-MSCs and BALB-MSCs were primed with the TLR agonist LPS isolated from E. coli 055:B5 and tested for their ability to inhibit bacterial growth ( Figure 1A, B ).…”

Section: Resultsmentioning

confidence: 99%

“…TLR4 priming, by exposing MSCs to bacterial lipopolysaccharide (LPS), causes widespread transcriptional changes primarily regulated by NF-κB and IRF1, and leads to the upregulation of genes involved with inflammatory response and chemotaxis 43 . Interestingly, LPS-primed MSCs have also been demonstrated to have enhanced antibacterial properties due to the upregulation of antimicrobial peptides 20,21,44 . Additionally, TLR4 has been identified as a critical receptor that promotes antibacterial activity in MSCs, and knockdown of this protein reduces the ability of MSCs to inhibit E. coli growth 21 .…”

Section: Introductionmentioning

confidence: 99%

Augmentation of Antibacterial Activity in Mesenchymal Stromal Cells Through Systems-Level Analysis and CRISPR-mediated Activation of CD14

Hirakawa

Tjahjono

Light

et al. 2020

Preprint

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Mesenchymal stromal cells (MSCs) have broad-ranging therapeutic capabilities, however MSC use is confounded by cell-to-cell heterogeneity, and source-to-source phenotypic inconsistencies. We utilized a systems-based approach to compare MSCs which displayed different capacity for antibacterial activity. Although MSCs from both sources satisfied traditional MSC-defining criteria, comparative transcriptomics and quantitative membrane proteomics demonstrated two unique molecular profiles. The antibacterial MSCs respond rapidly to bacterial lipopolysaccharide (LPS) and have elevated levels of the LPS co-receptor CD14. CRISPR-mediated overexpression of endogenous CD14 in non-antibacterial MSCs resulted in faster LPS response and enhanced antimicrobial activity. Single-cell transcriptome profiling of CD14-activated MSCs revealed uniform enhancement of LPS response kinetics, and a shift in the ground state of these MSCs. Our results demonstrate that systems-level analysis can reveal critical molecular targets to optimize desirable properties in MSCs, and that overexpression of CD14 in these cells can shift their state to be more responsive to future bacterial challenge.

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“…Antibacterial effect of MSCs is able to improve bacterial clearance through different mechanisms including phagocyte reprogramming (Krasnodembskaya et al, 2010;Mei et al, 2010), increasing the anaphylatoxin C5a concentration and an increase in monocytes phagocytic activity (Krasnodembskaya et al, 2012), secretion of antibacterial peptides, mitochondrial transfer to macrophages via the cytoplasmic bridges formation, EVs (Morrison et al, 2017) and the release of exosomes to increase their phagocytic index and mitochondrial metabolism (Jackson et al, 2016;Figure 3). (Saeedi, Halabian, & Fooladi, 2019a). Likewise, preconditioned MSCs with staphylococcal enterotoxin B increased the bacterial clearance and survival rate of sepsis model (Saeedi et al, 2019b).…”

Section: Impact Of Mscs On the Bacterial Burden In Sepsismentioning

confidence: 95%

Medicinal signaling cells: A potential antimicrobial drug store

Khatibi

Kheyrolahzadeh

Saadat

et al. 2020

Journal Cellular Physiology

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Medicinal signaling cells (MSCs) are multipotent cells derived from mammalian bone marrow and periosteum that can be extended in culture. They can keep their ability in vitro to form a variety of mesodermal phenotypes and tissues. Over recent years, there has been great attention over MSCs since they can impact the organ transplantation as well as autoimmune and bacterial diseases. MSCs can secrete different bioactive factors such as growth factors, antimicrobial peptides/proteins and cytokines that can suppress the immune system and prevent infection via direct and indirect mechanisms. Moreover, MSCs are able to increase bacterial clearance in sepsis models by producing antimicrobial peptides such as defensins, cathelicidins, lipocalin and hepcidin. It is the aim of the present review to focus on the antibacterial effector functions of MSCs and their mechanisms of action against the pathogenic microbes.

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Antimicrobial effects of mesenchymal stem cells primed by modified LPS on bacterial clearance in sepsis

Cited by 44 publications

References 35 publications

Therapeutic effects of curcumin on sepsis and mechanisms of action: A systematic review of preclinical studies

Therapeutic effects of curcumin on sepsis and mechanisms of action: A systematic review of preclinical studies

Augmentation of Antibacterial Activity in Mesenchymal Stromal Cells Through Systems-Level Analysis and CRISPR-mediated Activation of CD14

Medicinal signaling cells: A potential antimicrobial drug store

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