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      Umbilical cord blood stem cells transplantation as an adjunctive treatment strategy for liver cirrhosis in Chinese population: a meta-analysis of effectiveness and safety

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          Abstract

          Objective

          The aim of the study was to evaluate the efficacy and safety of umbilical cord blood stem cells (USCs) transplantation combined with routine supportive therapy (RST) for liver cirrhosis (LC).

          Materials and methods

          Clinical trials involved in this research were searched from Web of Science, PubMed, EMBASE, Cochrane Library, Wanfang and CNKI database. Treatment effects, quality of life (QoL), adverse events and other outcome measures were extracted and evaluated.

          Results

          A total of 10 trials including 616 LC patients were involved in this study. Based on our analysis, the liver function of LC patients was significantly improved after USCs transplantation and RST combined therapy, indicated by decreased total bilirubin, alanine aminotransferase, aspartate aminotransferase levels and prothrombin time and increased serum albumin level and prothrombin activity. Compared to those treated by RST alone, patients treated by combined therapy showed more satisfied treatment effects, improved QoL reflected by improved appetite (odds ratio [OR]=5.43, 95% CI=2.84 to 10.38, P<0.00001) and relieved fatigue (OR=4.33, 95% CI=0.87 to 21.60, P=0.07), ascetic fluid (OR=4.56, 95% CI=2.69 to 7.74, P<0.00001), abdominal distension (OR=4.01, 95% CI=1.34 to 12.02, P=0.01) and edema (OR=2.69, 95% CI=0.23 to 31.72, P=0.43). No serious adverse events occurred during USCs therapy.

          Conclusion

          USCs transplantation is a safe and effective adjuvant therapy for RST-treated LC, possibly through improving patients’ liver function.

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          Most cited references 45

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          Quantifying the impact of between-study heterogeneity in multivariate meta-analyses

          Measures that quantify the impact of heterogeneity in univariate meta-analysis, including the very popular I 2 statistic, are now well established. Multivariate meta-analysis, where studies provide multiple outcomes that are pooled in a single analysis, is also becoming more commonly used. The question of how to quantify heterogeneity in the multivariate setting is therefore raised. It is the univariate R 2 statistic, the ratio of the variance of the estimated treatment effect under the random and fixed effects models, that generalises most naturally, so this statistic provides our basis. This statistic is then used to derive a multivariate analogue of I 2, which we call . We also provide a multivariate H 2 statistic, the ratio of a generalisation of Cochran's heterogeneity statistic and its associated degrees of freedom, with an accompanying generalisation of the usual I 2 statistic, . Our proposed heterogeneity statistics can be used alongside all the usual estimates and inferential procedures used in multivariate meta-analysis. We apply our methods to some real datasets and show how our statistics are equally appropriate in the context of multivariate meta-regression, where study level covariate effects are included in the model. Our heterogeneity statistics may be used when applying any procedure for fitting the multivariate random effects model. Copyright © 2012 John Wiley & Sons, Ltd.
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            Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients.

            Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord-derived MSC (UC-MSC) in patients with decompensated LC. A total of 45 chronic hepatitis B patients with decompensated LC, including 30 patients receiving UC-MSC transfusion, and 15 patients receiving saline as the control, were recruited; clinical parameters were detected during a 1-year follow-up period. No significant side-effects and complications were observed in either group. There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls (P < 0.05). UC-MSC therapy also significantly improved liver function, as indicated by the increase of serum albumin levels, decrease in total serum bilirubin levels, and decrease in the sodium model for end-stage liver disease scores. UC-MSC transfusion is clinically safe and could improve liver function and reduce ascites in patients with decompensated LC. UC-MSC transfusion, therefore, might present a novel therapeutic approach for patients with decompensated LC. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
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              Immunomodulation of activated hepatic stellate cells by mesenchymal stem cells.

              Bone marrow-derived mesenchymal stem cells (MSCs) have been reported to prevent the development of liver fibrosis in a number of pre-clinical studies. Marked changes in liver histopathology and serological markers of liver function have been observed without a clear understanding of the therapeutic mechanism by which stem cells act. We sought to determine if MSCs could modulate the activity of resident liver cells, specifically hepatic stellate cells (SCs) by paracrine mechanisms using indirect cocultures. Indirect coculture of MSCs and activated SCs led to a significant decrease in collagen deposition and proliferation, while inducing apoptosis of activated SCs. The molecular mechanisms underlying the modulation of SC activity by MSCs were examined. IL-6 secretion from activated SCs induced IL-10 secretion from MSCs, suggesting a dynamic response of MSCs to the SCs in the microenvironment. Blockade of MSC-derived IL-10 and TNF-alpha abolished the inhibitory effects of MSCs on SC proliferation and collagen synthesis. In addition, release of HGF by MSCs was responsible for the marked induction of apoptosis in SCs as determined by antibody-neutralization studies. These findings demonstrate that MSCs can modulate the function of activated SCs via paracrine mechanisms provide a plausible explanation for the protective role of MSCs in liver inflammation and fibrosis, which may also be relevant to other models of tissue fibrosis.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2018
                26 February 2018
                : 14
                : 417-440
                Affiliations
                [1 ]Department of Gastroenterology, Liaocheng People’s Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong Province, People’s Republic of China
                [2 ]Department of Health Care, Weifang People’s Hospital, Weifang, Shandong Province, People’s Republic of China
                [3 ]Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong Province, People’s Republic of China
                Author notes
                Correspondence: Changhui Zhou, Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng Clinical School of Taishan Medical University, Dongchang West Road, No 67, Liaocheng 252000, Shandong Province, People’s Republic of China, Tel +86 135 6207 8772, Email zhouch2006@ 123456163.com
                [*]

                These authors contributed equally to this work

                Article
                tcrm-14-417
                10.2147/TCRM.S157603
                5834176
                © 2018 Tao et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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