Mesenchymal stem cells regulate hepatocytes excessive autophagy and apoptosis through miR-125b/TRAF6 pathway in acute-on-chronic liver failure

2020 ◽  
Vol 73 ◽  
pp. S500
Author(s):  
Dengna Lin ◽  
Bingliang Lin ◽  
Jing Zhang ◽  
Jing Xiong ◽  
Juan Gao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Failure ◽  
Chronic Liver ◽  
Chronic Liver Failure

Human mesenchymal stem cells for hepatitis B virus-related acute-on-chronic liver failure

2018 ◽  
Vol 30 (10) ◽  
pp. 1224-1229 ◽  
Author(s):  
Bin Chen ◽  
Yong-Hong Wang ◽  
Jin-Qin Qian ◽  
Dong-Bo Wu ◽  
En-Qiang Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Liver Failure ◽  
Human Mesenchymal Stem Cells ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
B Virus

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

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Fernando Comunello Schacher ◽  
Annelise Martins Pezzi da Silva ◽  
Lucia Mariano da Rocha Silla ◽  
Mario Reis Álvares-da-Silva
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Liver Failure ◽  
Phase I ◽  
Intervention Group ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Marrow Mesenchymal Stem Cells ◽  
Cirrhotic Patients

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.

Mesenchymal stem cells regulated DX5 – liver natural killer cells in rescuing acute-on-chronic liver failure murine

2020 ◽  
Vol 73 ◽  
pp. S491
Author(s):  
Jing Xiong ◽  
Bingliang Lin ◽  
Zhiliang Gao ◽  
Shi Qiu Xiong ◽  
Weizhen Weng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Natural Killer Cells ◽  
Liver Failure ◽  
Natural Killer ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Killer Cells

scholarly journals The impact of recipient age on the effects of umbilical cord mesenchymal stem cells on HBV-related acute-on-chronic liver failure and liver cirrhosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ka Zhang ◽  
Haixia Sun ◽  
Huijuan Cao ◽  
Yifan Jia ◽  
Xin Shu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Liver Failure ◽  
Chronic Liver ◽  
Therapeutic Effects ◽  
Chronic Liver Failure ◽  
Group A ◽  
Recipient Age ◽  
Group D

Abstract Background The results of a previous study verified that umbilical cord mesenchymal stem cells (UCMSCs) have good therapeutic effects for the treatment of HBV-related acute-on-chronic liver failure (ACLF) and liver cirrhosis (LC). Nevertheless, it is still unknown whether the effects of UCMSCs are affected by recipient age. Methods Patients treated with UCMSCs who met the criteria of HBV-related ACLF and liver cirrhosis were identified in this retrospective observational study. Patients were divided into subgroups according to the World Health Organization (WHO) age criteria (< 45 vs. ≥ 45 years). Group A included young ACLF patients (< 45 y), and group B included older ACLF patients (≥ 45 y). Young LC patients (< 45 y) were assigned to group C, and group D included older LC patients (≥ 45 y). Patients’ clinical characteristics, demographics, biochemical factors, and model for end-stage liver disease (MELD) scores were compared for 24 weeks. Results Sixty-four ACLF patients and 59 LC patients were enrolled in this study. Compared with patients in groups B and C, patients in group A did not show significant superiority in terms of the levels of ALT, AST, TBIL, AFP, and PTA and MELD scores. However, the median decrease and cumulative decrease in the TBIL and ALT levels of patients in group C were larger than those of patients in group D after four weeks of UCMSC transfusions. For older patients (≥ 45 y), the cumulative decrease and the median decrease in the TBIL of ACLF patients were significantly greater than those of LC patients after UCMSC treatment. However, the median decrease in ALT levels of ACLF patients was significantly greater than that of LC patients during UCMSC treatment, and the cumulative decrease in ALT levels of ACLF patients was significantly greater than that of LC patients at all time points. Conclusion The therapeutic effects of UCMSCs for HBV-related acute-on-chronic liver failure and liver cirrhosis varied partly by patient age. Assessing patient age is necessary prior to UCMSC clinical use.

Mesenchymal stem cells for hepatitis B patients with acute on chronic liver failure—are we there?

Hepatology ◽  
2017 ◽  
Vol 66 (5) ◽  
pp. 1705-1706 ◽  
Author(s):  
Wuttiporn Manatsathit ◽  
Hrishikesh Samant ◽  
Warapan Nakayuenyongsuk
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hepatitis B ◽  
Liver Failure ◽  
Chronic Liver ◽  
Chronic Liver Failure

scholarly journals Mesenchymal stem cells regulated liver DX5- natural killer cells in acute-on-chronic liver failure

2020 ◽  
Author(s):  
Jing Xiong ◽  
Weizhen Weng ◽  
Dengna Lin ◽  
Huijuan Cao ◽  
Junfeng Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Mesenchymal Stem Cells ◽  
Liver Failure ◽  
Nk Cells ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Gm Csf

Abstract Background :Acute-on-chronic liver failure (ACLF) is a severe, life-threatening syndrome with high mortality. Transplantation of Mesenchymal Stem Cells (MSCs) have been shown their efficacy in reducing mortality of ACLF patients in our clinical trials. Unveiling the underlying mechanism of action will improve clinical regime of ACLF. Methods: Flow cytometry was applied to assess frequency and phenotype of peripheral blood natural killer cell (NK) from HBV-ACLF patients during MSCs treatment. An acute-on-chronic liver failure mouse model was established by injection of carbon tetrachloride (CCL4) intraperitoneally. We used flow cytometry to characterize frequency, phenotype, proliferation, cytokine secretion and cell conjugation of NK cells from different sources before and after MSCs treatment. Microscopy was applied to investigate cell-cell contact. Results: Frequency of peripheral blood NK cells from HBV-ACLF patients was upregulated by MSCs infusion, which correlated with hepatitis remission. MSCs infusion rescued ACLF mice efficiently, coinciding with hepatitis remission, liver regeneration and NK cells frequency increase both in blood and liver. Strikingly, NKP46+ DX5-, instead of NKP46+ DX5+ liver NK cells responded well to MSCs. In vitro, MSCs were proved to promote the proliferation and GM-CSF secretion of NKP46+ DX5- liver NK cells specifically, which may be owing to their high cell-cell adhesion. Conclusions: Promoting NKP46+ DX5- liver NK cells proliferation and secreting GM-CSF maybe the new machinery of MSCs’ efficacy in ACLF.

A Brief Analysis of Mesenchymal Stem Cells as Biological Drugs for the Treatment of Acute-on-Chronic Liver Failure (ACLF): Safety and Potency

2020 ◽  
Vol 15 (3) ◽  
pp. 202-210
Author(s):  
Ying Feng ◽  
Ai-Tong Wang ◽  
Hong-Hong Jia ◽  
Meng Zhao ◽  
Hao Yu
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Liver Failure ◽  
Immunosuppressive Drugs ◽  
Chronic Liver ◽  
Research Progress ◽  
Comprehensive Treatment ◽  
Chronic Liver Failure ◽  
Biological Drugs

Acute-on-Chronic Liver Failure (ACLF) is characterized by acute exacerbation of chronic hepatitis, organ failure, high mortality, and poor prognosis. At present, the clinical methods of treatment include comprehensive treatment with medicines, artificial liver system, and Orthotopic Liver Transplantation (OLT), and of these, OLT is considered the most effective treatment for ACLF. However, it is difficult for ACLF patients to benefit from OLT due to the shortage of liver donors, high cost, unpredictable postoperative complications, and long-term use of immunosuppressive drugs; therefore, it is important to explore a new treatment option. With the development of stem cell transplantation technology in recent years, several studies have shown that treatment of ACLF with Mesenchymal Stem Cells (MSCs) leads to higher survival rates, and has good tolerance and safety rates, thereby improving the liver function and quality of life of patients; it has also become one of the popular research topics in clinical trials. This paper summarizes the current clinical interventions and treatments of ACLF, including the clinical trials, therapeutic mechanisms, and research progress on MSC application in the treatment of ACLF. The problems and challenges of the development of MSC-based therapy in the future are also discussed.

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