scholarly journals Human umbilical cord-derived mesenchymal stem cells improve the function of liver in rats with acute-on-chronic liver failure via downregulating Notch and Stat1/Stat3 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yulin He ◽  
Xingrong Guo ◽  
Tingyu Lan ◽  
Jianbo Xia ◽  
Jinsong Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sodium Chloride ◽  
Inflammatory Cell ◽  
Serum Levels ◽  
Chronic Liver ◽  
Human Umbilical Cord ◽  
Chronic Liver Failure ◽  
Stat3 Signaling ◽  
Liver Tissues

Abstract Background Effective treatments for acute-on-chronic liver failure (ACLF) are lacking. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been applied in tissue regeneration and repair, acting through paracrine effects, cell fusion, and actual transdifferentiation. The present study was designed to investigate the therapeutic potential of hUC-MSCs in acute-on-chronic liver injury (ACLI) and ACLF rat models. Methods Wistar rats aged 6 weeks were intraperitoneally administered porcine serum (PS) at a dose of 0.5 mL twice per week for 11 weeks to generate an immune liver fibrosis model. After 11 weeks, rats with immune liver fibrosis were injected intravenously with lipopolysaccharide (LPS) to induce an ACLI model or combined LPS and D-galactosamine (D-GalN) to induce an ACLF model. The rats with ACLI or ACLF were injected intravenously with 2×106 hUC-MSCs, 4×106 hUC-MSCs, or 0.9% sodium chloride as a control. The rats were sacrificed at 1, 2, 4, and 6 weeks (ACLI rats) or 4, 12, and 24 h (ACLF rats). The blood and liver tissues were collected for biochemical and histological investigation. Results The application of hUC-MSCs in rats with ACLI and ACLF led to a significant decrease in the serum levels of ALT, AST, TBil, DBil, ALP, ammonia, and PT, with ALB gradually returned to normal levels. Inflammatory cell infiltration and collagen fiber deposition in liver tissues were significantly attenuated in ACLI rats that received hUC-MSCs. Inflammatory cell infiltration and apoptosis in liver tissues of ACLF rats that received hUC-MSCs were significantly attenuated. Compared with those in the rats that received 0.9% sodium chloride, a significant reduction in proinflammatory cytokine levels and elevated serum levels of hepatocyte growth factor (HGF) were found in ACLF rats that received hUC-MSCs. Furthermore, Notch, IFN-γ/Stat1, and IL-6/Stat3 signaling were inhibited in ACLI/ACLF rats that received hUC-MSCs. Conclusions hUC-MSC transplantation can improve liver function, the degree of fibrosis, and liver damage and promote liver repair in rats with ACLI or ACLF, mediated most likely by inhibiting Notch signaling and reversing the imbalance of the Stat1/Stat3 pathway.

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 potential therapeutic effect for melatonin and mesenchymal stem cells on hepatocellular carcinoma

BioMedicine ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 24 ◽  
Author(s):  
Yasser Mohamed ◽  
Mohamed A. Basyony ◽  
Nabila I. El-Desouki ◽  
Walied S. Abdo ◽  
Mohammed A. El-Magd
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Effect ◽  
Therapeutic Potential ◽  
Combined Treatment ◽  
Elevated Serum ◽  
Liver Weight ◽  
Serum Levels ◽  
Caspase 9 ◽  
Liver Tissues

Background/aim: Herein, we investigated the potential therapeutic effect of Melatonin (Mel) and/or mesenchymal stem cells (MSCs) on rat model of HCC. Materials and Methods: Female mature rats were divided into 5 groups (n = 10/group): normal (Nor), HCC group intraperitoneally injected with 200 mg/kg DEN, and 3 treated groups; HCC + Mel (Mel) group given Mel intraperitoneally 20 mg/kg, twice a week, HCC + MSCs (MSCs) group intravenously injected by 1 × 106 cells, and HCC + MSCs (Mel +MSCs) group. Results: Rats in HCC group showed most deteriorated effect in form of increased mortality and relative liver weight, elevated serum levels of ALT, AST, ALP, AFP and GGT in addition to increased pre-neoplastic nodules in liver tissues. Liver tissues of HCC group also exhibited lower level of apoptosis as indicated by decreased DNA fragmentation and expression of p53 caspase 9 and caspase 3 genes and increased PCNA immunoreactivity. Moreover, in this group the expression of IL6 and TGFβ1 genes was significantly upregulated. All these deleterious effects induced by DEN were reversed after administration of Mel and/ or MSCs with best improvement for the combined group (MSCs + Mel). Conclusions: These findings reveal a better therapeutic effect for MSCs when given with Mel and we attribute this beneficial effect, at least in part, to triggering apoptosis and targeting inflammation in HCC. Therefore, combined treatment with Mel and MSCs is recommended to enhance the therapeutic potential against HCC.

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
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