scholarly journals Human Amnion-Derived Mesenchymal Stromal Cells: A New Potential Treatment for Carbapenem-Resistant Enterobacterales in Decompensated Cirrhosis

2022 ◽  
Vol 23 (2) ◽  
pp. 857
Author(s):  
Mariangela Pampalone ◽  
Giampiero Vitale ◽  
Salvatore Gruttadauria ◽  
Giandomenico Amico ◽  
Gioacchin Iannolo ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Bacterial Load ◽  
Phenotypic Expression ◽  
Decompensated Cirrhosis ◽  
Resistant Bacteria ◽  
Complement Protein ◽  
In Vivo Models ◽  
Carbapenem Resistant ◽  
Anti Inflammatory

Background: Spontaneous bacterial peritonitis (SBP) is a severe and often fatal infection in patients with decompensated cirrhosis and ascites. The only cure for SBP is antibiotic therapy, but the emerging problem of bacterial resistance requires novel therapeutic strategies. Human amniotic mesenchymal stromal cells (hA-MSCs) possess immunomodulatory and anti-inflammatory properties that can be harnessed as a therapy in such a context. Methods: An in vitro applications of hA-MSCs in ascitic fluid (AF) of cirrhotic patients, subsequently infected with carbapenem-resistant Enterobacterales, was performed. We evaluated the effects of hA-MSCs on bacterial load, innate immunity factors, and macrophage phenotypic expression. Results: hA-MSCs added to AF significantly reduce the proliferation of both bacterial strains at 24 h and diversely affect M1 and M2 polarization, C3a complement protein, and ficolin 3 concentrations during the course of infection, in a bacterial strain-dependent fashion. Conclusion: This study shows the potential usefulness of hA-MSC in treating ascites infected with carbapenem-resistant bacteria and lays the foundation to further investigate antibacterial and anti-inflammatory roles of hA-MSC in in vivo models.

Abstract WP88: In a Pro-inflammatory Environment, Mesenchymal Stromal Cells Exert Anti-inflammatory and Pro-angiogenic Effects on Endothelial Cells

Stroke ◽  
2018 ◽  
Vol 49 (Suppl_1) ◽  
Author(s):  
Kaavya Giridhar ◽  
Nikunj Satani ◽  
Bing Yang ◽  
Songmi Lee ◽  
Xiaopei Xi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Anti Inflammatory

Transient ectopic expression of CXCR4 and IL10 enhances in vivo anti-inflammatory potential of human mesenchymal stromal cells

Cytotherapy ◽  
2020 ◽  
Vol 22 (5) ◽  
pp. S60
Author(s):  
M. Hervas-Salcedo ◽  
M. Fernandez-Garcia ◽  
M. Hernando-Rodriguez ◽  
Ó. Quintana ◽  
J. Segovia ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ectopic Expression ◽  
Human Mesenchymal Stromal Cells ◽  
Anti Inflammatory

scholarly journals Preconditioning in an Inflammatory Milieu Augments the Immunotherapeutic Function of Mesenchymal Stromal Cells

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 462 ◽  
Author(s):  
Luis A. Rodriguez ◽  
Arezoo Mohammadipoor ◽  
Lucero Alvarado ◽  
Robin M. Kamucheka ◽  
Amber M. Asher ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Comprehensive Evaluation ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Human Mscs ◽  
Post Injury ◽  
Anti Inflammatory ◽  
And Function ◽  
Inflammatory Milieu

Multipotent mesenchymal stromal cells (MSCs) have emerged as potent therapeutic agents for multiple indications. However, recent evidence indicates that MSC function is compromised in the physiological post-injury milieu. In this study, bone marrow (BM)- and adipose-derived (AD)-MSCs were preconditioned in hypoxia with or without inflammatory mediators to potentiate their immunotherapeutic function in preparation for in vivo delivery. Human MSCs were cultured for 48 h in either normoxia (21% O2) or hypoxia (2% O2) with or without the addition of Cytomix, thus creating 4 groups: (1) normoxia (21%); (2) Cytomix-normoxia (+21%); (3) hypoxia (2%); and (4) Cytomix-hypoxia (+2%). The 4 MSC groups were subjected to comprehensive evaluation of their characteristics and function. Preconditioning did not alter common MSC surface markers; nonetheless, Cytomix treatment triggered an increase in tissue factor (TF) expression. Moreover, the BM-MSCs and AD-MSCs from the +2% group were not able to differentiate to chondrocytes and osteoblasts, respectively. Following Cytomix preconditioning, the metabolism of MSCs was significantly increased while viability was decreased in AD-MSCs, but not in BM-MSCs. MSCs from both tissues showed a significant upregulation of key anti-inflammatory genes, increased secretion of IL-1 receptor antagonist (RA), and enhanced suppression of T-cell proliferation following the Cytomix treatment. Similarly, following a lipopolysaccharide challenge, the Cytomix-treated MSCs suppressed TNF-α secretion, while promoting the production of IL-10 and IL-1RA. These preconditioning approaches facilitate the production of MSCs with robust anti-inflammatory properties. AD-MSCs preconditioned with Cytomix under normoxia appear to be the most promising therapeutic candidates; however, safety concerns, such as thrombogenic disposition of cells due to TF expression, should be carefully considered prior to clinical translation.

scholarly journals Placental Mesenchymal Stromal Cells (PMSCs) and PMSC-Derived Extracellular Vesicles (PMSC-EVs) Attenuated Renal Fibrosis in Rats with Unilateral Ureteral Obstruction (UUO) by Regulating CD4+ T Cell Polarization

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Zhu Zhu ◽  
Chaonan Han ◽  
Shuli Xian ◽  
Feng Zhuang ◽  
Feng Ding ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Cell Infiltration ◽  
Inflammatory Factors ◽  
Anti Inflammatory

Purpose. Recent evidence has shown that CD4+ T helper (Th) cells are involved in renal inflammation and fibrosis. However, whether renal fibrosis can be alleviated by intervening in the polarization of CD4+ T cells remains unknown. Our research investigated the effects of intravenously administered placenta mesenchymal stromal cells (PMSCs) or treatment with extracellular EVs (EVs) derived from PMSCs (PMSC-EVs) on the polarization of CD4+ T cells in rats with unilateral ureteral obstruction (UUO). We further verified how PMSCs affect inflammatory factor secretion and the levels of regulatory T (Treg) and Th17 CD4+ T cells in vitro. Materials and Methods. We evaluated renal interstitial inflammation and fibrosis by pathological section staining, tested the polarization of CD4+ T cells (Th17 and Treg phenotypes) by flow cytometry (FCM) and immunohistochemistry, and detected the cytokines secreted by CD4+ T cells by enzyme-linked immunosorbent assay (ELISA). Results. Compared with that of control rats, the renal tissue of PMSC-treated rats exhibited lower renal Masson scores and more Foxp3+ cell infiltration, with a significantly decreased IL17A+CD4+ T cell/CD4+ T cell ratio and a significantly elevated anti-inflammatory cytokine (IL-10) level. When CD4+ T cells were cocultured with PMSCs, CD4+IL17A+ cell percentages were decreased in a UUO model after 7 days of coculture with PMSCs. The secretion of TGF-β and IL-10 was significantly increased (P<0.05), while the secretion of IFN-γ, IL-17, and IL-6 was significantly decreased (P<0.05) in the PMSC coculture group. Moreover, after treatment with PMSC-EVs, tubulointerstitial fibrosis was alleviated, and Foxp3+/IL-17+ cell infiltration was increased in the kidneys of UUO model animals on day 7. Conclusions. PMSCs can convert the inflammatory environment into an anti-inflammatory environment by affecting the polarization of CD4+ T cells and macrophages, inhibiting the inflammatory factors IFN-γ and IL-17, and upregulating the expression of the anti-inflammatory factors TGF-β and IL-10, ultimately leading to renal protection. Such functions may be mediated by the paracrine activity of PMSC-EVs.

scholarly journals In vivo studies on antibiotic combination for the treatment of carbapenem-resistant Gram-negative bacteria: a systematic review and meta-analysis protocol

2020 ◽  
Vol 4 (1) ◽  
pp. e100055
Author(s):  
Elda Righi ◽  
Luigia Scudeller ◽  
Margherita Chiamenti ◽  
Kamilia Abdelraouf ◽  
Thomas Lodise ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
In Vivo Models ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
The Impact ◽  
Antibiotic Combination

ObjectiveThere is poor evidence to determine the superiority of combination regimens versus monotherapy against infections due to carbapenem-resistant (CR) Gram-negative bacteria. In vivo models can simulate the pathophysiology of infections in humans and assess antibiotic efficacy. We aim to investigate in vivo effects of antibiotic combination on mortality and disease burden for infections due to CR Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae and provide an unbiased overview of existing knowledge. The results of the study can help prioritising future research on the most promising therapies against CR bacteria.Methods and analysisThis protocol was formulated using the Systematic Review Protocol for Animal Intervention Studies (SYRCLE) Checklist. Publications will be collected from PubMed, Scopus, Embase and Web of Science. Quality checklists adapted by Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies and SYRCLE’s risk of bias tool will be used. If the meta-analysis seems feasible, the ES and the 95% CI will be analysed. The heterogeneity between studies will be assessed by I2 test. Subgroup meta-analysis will be performed when possible to assess the impact of the studies on efficacy of the treatments. Funnel plotting will be used to evaluate the risk of publication bias.DisseminationThis systematic review and meta-analysis is part of a wider research collaboration project, the COmbination tHErapy to treat sepsis due to carbapenem-Resistant bacteria in adult and paediatric population: EvideNCE and common practice (COHERENCE) study that includes also the analyses of in vitro and human studies. Data will be presented at international conferences and the results will be published in peer-reviewed journals.PROSPERO registration numberCRD42019128104(available at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019128104).

scholarly journals Human Amnion-Derived Mesenchymal Stromal Cells in Cirrhotic Patients with Refractory Ascites: A Possible Anti-Inflammatory Therapy for Preventing Spontaneous Bacterial Peritonitis

2021 ◽  
Author(s):  
Mariangela Pampalone ◽  
Simona Corrao ◽  
Giandomenico Amico ◽  
Giampiero Vitale ◽  
Rossella Alduino ◽  
...  
Keyword(s):  
Ascitic Fluid ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Spontaneous Bacterial Peritonitis ◽  
Refractory Ascites ◽  
M2 Macrophage ◽  
Human Amnion ◽  
Bacterial Peritonitis ◽  
Cirrhotic Patients ◽  
Anti Inflammatory

AbstractCirrhosis is associated with dysregulated immune cell activation and immune dysfunction. These conditions modify gut flora, facilitate bacterial translocation, and increase susceptibility to bacterial peritonitis and consequent systemic infections by dramatically affecting long-term patient survival. Human amnion-derived mesenchymal stromal cells (hA-MSCs) exert immunomodulatory potential benefit, and have the ability to modulate their actions, especially in situations requiring immune activation through mechanisms not fully understood. In this study, we aimed to investigate, in vitro, the immunostimulant or immunosuppressive effects of hA-MSCs on cellular components of ascitic fluid obtained from cirrhotic patients with refractory ascites. We found that hA-MSCs viability is not affected by ascitic fluid and, interestingly, hA-MSCs diminished the pro-inflammatory cytokine production, and promoted anti-inflammatory M2 macrophage polarization. Moreover, we found that there was no simultaneous significant decrease in the M1-like component, allowing a continual phagocytosis activity of macrophages and NK cells to restore a physiological condition. These data highlight the plasticity of hA-MSCs’ immunomodulatory capacity, and pave the way to further understanding their role in conditions such as spontaneous bacterial peritonitis. Graphical abstract

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