Injured hepatocyte-released microvesicles induce bone marrow-derived mononuclear cells differentiation

Simon, Laura; López, Mónica Luján; Cruz, Carolina Uribe; Vergara, Davi Fernandes Peralvo; Silla, Lúcia Mariano da Rocha; Matte, Úrsula

doi:10.1016/j.diff.2015.09.001

Cited by 5 publications

(2 citation statements)

References 31 publications

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“…Lin et al [18] also treated patients with BM-MSC in a different protocol (1 infusion per week for 4 weeks). Our research group has been working on MSC in other scenarios [29][30][31][32], especially in acute graft-versushost disease [33,34] with good results. Based on these previous studies, we hypothesize that a similar protocol might be able to change the course of ACLF.…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow Mesenchymal Stem Cells in Acute-on-Chronic Liver Failure Grades 2 and 3: A Phase I-II Randomized Clinical Trial

Schacher

Silva

Silla

et al. 2021

Canadian Journal of Gastroenterology and Hepatology

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Introduction. Acute-on-chronic liver failure (ACLF) is an acute liver decompensation in cirrhotic patients, which leads to organ failures and high short-term mortality. The treatment is based on the management of complications and, in severe cases, liver transplantation. Since specific treatment is unavailable, we aimed to evaluate the safety and initial efficacy of bone marrow mesenchymal stem cells (BM-MSC) in patients with ACLF Grades 2 and 3, a population excluded from previous clinical trials. Methods. This is a randomized placebo-controlled phase I-II single center study, which enrolled 9 cirrhotic patients from 2018 to 2020, regardless of the etiology. The control group (n = 5) was treated with standard medical therapy (SMT) and placebo infusion of saline. The intervention group (n = 4) received SMT plus 5 infusions of 1 × 106 cells/kg of BM-MSC for 3 weeks. Both groups were monitored for 90 days. A Chi-square test was used for qualitative variables, and the t-test and Mann–Whitney U test for quantitative variables. The Kaplan–Meier estimator was used to build survival curves. In this study, we followed the intention-to-treat analysis, with a significance of 5%. Results. Nine patients with a mean Child–Pugh (CP) of 12.3, MELD of 38.4, and CLIF-C score of 50.7 were recruited. Hepatitis C and alcohol were the main etiologies. The average infusion per patient was 2.9 and only 3 patients (2 in control and 1 in the BM-MSC group) received all the protocol infusions. There were no infusion-related side effects, although one patient in the intervention group presented hypernatremia and a gastric ulcer, after the third and fifth infusions, respectively. The survival rate after 90 days was 20% (1/5) for placebo versus 25% (1/4) for the BM-MSC. The patient who completed the entire MSC protocol showed a significant improvement in CP (C-14 to B-9), MELD (32 to 22), and ACLF (grade 3 to 0). Conclusion. BM-MSC infusion is safe and feasible in patients with ACLF Grades 2 and 3.

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Section: Discussionmentioning

confidence: 99%

Bone Marrow Mesenchymal Stem Cells in Acute-on-Chronic Liver Failure Grades 2 and 3: A Phase I-II Randomized Clinical Trial

Schacher

Silva

Silla

et al. 2021

Canadian Journal of Gastroenterology and Hepatology

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“…Hepatocyte-like characteristics were observed in the non-adherent bone marrow-derived mononuclear cells after 24h of co-culture with injured hepatocytes. Microvesicles derived from differentiated cells revealed the presence of hepatocyte-specific mRNAs, including albumin, coagulation factor V, alpha-fetoprotein, and cytokeratin 18, suggesting a possible role in the induction of cell plasticity (Simon et al, 2015). Circulating miRNAs in serum exosomes have potential as novel biomarkers for predicting HCC recurrence.…”

Section: Extracellular Vesicles Alterations In Liver Diseasesmentioning

confidence: 99%

Extracellular vesicles: Novel mediator for cell to cell communications in liver pathogenesis

Devhare

Ray

2018

Molecular Aspects of Medicine

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Extracellular vesicles (EVs) are membrane derived nanometer-sized vesicles. EVs are released by normal, diseased, and transformed cells in vitro and in vivo, and carry lipids, proteins, mRNAs, non-coding RNAs, and even DNA out of cells. Transferring biological information via EVs to neighboring cells and inter-cellular communication not only maintain physiological functions, but also involve in the pathogenesis of several diseases, including cancer. The aim of this review is to discuss the emerging role of EVs in viral hepatitis, non-alcoholic or alcoholic liver disease and liver cancers. We summarize what is known about exosome biogenesis, and role in liver disease progression, and discuss the potential clinical applications of EVs as predictive biomarkers and therapeutic modalities.

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Liver-derived extracellular vesicles: A cell by cell overview to isolation and characterization practices

Zivko

Fuhrmann

Luciani

2021

Biochimica et Biophysica Acta (BBA) - General Subjects

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BACKGROUND: Extracellular vesicles (EVs) are a diverse group of membrane-bound nanovesicles potentially released by every cell. With the liver's unique ensemble of cells and its fundamental physiological tasks, elucidating the role of EV-mediated hepatic cellular crosstalk and their role in different pathologies has been gaining the attention of many scientists. SCOPE OF REVIEW: The present review shifts the perspective into practice: we aim to critically discuss the methods used to purify and to biochemically analyse EVs from specific liver resident cells, including hepatocytes, hepatic stellate cells, cholangiocytes, liver sinusoidal endothelial cells, Kupffer cells, liver stem cells. The review offers a reference guide to current approaches. MAJOR CONCLUSIONS: Strategies for EV isolation and characterization are as varied as the research groups performing them. We present main advantages and disadvantages for the methods, highlighting common causes for concern, such as FBS handling, reporting of cell viability, EV yield and storage, differences in differential centrifugations, suboptimal method descriptions, and method transferability. We both looked at how adaptable the research between human and rodent cells in vitro is, and also assessed how well either of them translates to ex vivo settings. GENERAL SIGNIFICANCE: We reviewed methodological practices for the isolation and analysis of liver-derived EVs, making a cell type specific user guide that shows where to start, what has worked so far and to what extent. We critically discussed room for improvement, placing a particular focus on working towards a potential standardization of methods.

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Injured hepatocyte-released microvesicles induce bone marrow-derived mononuclear cells differentiation

Cited by 5 publications

References 31 publications

Bone Marrow Mesenchymal Stem Cells in Acute-on-Chronic Liver Failure Grades 2 and 3: A Phase I-II Randomized Clinical Trial

Bone Marrow Mesenchymal Stem Cells in Acute-on-Chronic Liver Failure Grades 2 and 3: A Phase I-II Randomized Clinical Trial

Extracellular vesicles: Novel mediator for cell to cell communications in liver pathogenesis

Liver-derived extracellular vesicles: A cell by cell overview to isolation and characterization practices

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