scholarly journals The Role of Bone Marrow Mesenchymal Stem Cells in the Treatment of Acute Liver Failure

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Shufang Yuan ◽  
Tao Jiang ◽  
Lihua Sun ◽  
Rongjiong Zheng ◽  
Nizam Ahat ◽  
...  

Objective.This study is to investigate the effects of bone marrow mesenchymal stem cell (BMSC) transplantation on acute liver failure (ALF).Methods.BMSCs were separated from rat bone marrow, cultured, and identified by flow cytometry. Rat model with ALF was established by injecting D-galactosamine and lipopolysaccharide. Rats were randomly divided into the control group and BMSC transplantation group. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at 24 h, 120 h, and 168 h after BMSC transplantation. Apoptosis was detected by TUNEL assay. The expression of VEGF and AFP proteins was detected by immunofluorescence. Caspase-1 and IL-18 proteins and mRNA were detected by immunohistochemistry and RT-PCR.Results.Compared with the control group, levels of ALT, AST, caspase-1 and IL-18 proteins, and mRNA in the transplantation group were significantly lower at 120 h and 168 h after BMSCs transplantation. Apoptosis was inhibited by BMSCs transplantation. The VEGF protein levels were increased with the improvement of liver function, and the AFP protein levels were increased with the deterioration of the liver function after BMSCs transplantation.Conclusions.BMSCs transplantation can improve liver function and inhibit hepatocyte apoptosis as well as promote hepatocyte proliferation in rat model with ALF.

2021 ◽  
Author(s):  
Yichi Zhang ◽  
Xinsheng Nie ◽  
Lijuan Wang ◽  
Zhuzhi Wan ◽  
Hao Jin ◽  
...  

Abstract BackgroundLiver cirrhosis, which lacks a specific therapy, induces a substantial economic burden and affects quality of life. Exosomes are nanosized vesicles that are secreted by cells transfer bioactive molecules to regulate metastasis and have attracted immense interest as a therapeutic option for liver cirrhosis. Therefore, in this study, we explored the efficacy and dose of exosomes derived from rat bone marrow mesenchymal stem cells (Exos-rBMMSC) in a hepatic cirrhosis rat model. ResultsFour weeks after exosome therapy, NLRP3, GSDMD, cleaved caspase-1, IL-1β and IL-18 expression levels in the 200 μg and 400 μg Exos-rBMMSC groups were significantly decreased compared to those in the liver cirrhosis group (P<0.05). Similar results were observed in the hepatic function assay; serum levels of aspartate aminotransferase and alanine aminotransferase were decreased, and albumin was increased. The histopathology results showed that 200 μg and 400 μg of Exos-rBMMSC significantly relieved collagen deposition, while 100 μg of Exos-rBMMSC induced no marked improvements compared to those in the liver cirrhosis group. The localization of PKH67-labelled Exos-rBMMSC was verified microscopically, and these particles coexpressed PCNA, NLRP3, GSDMD and Caspase-1. ConclusionsOur findings suggest that Exos-rBMMSC accelerate hepatocyte proliferation and relieve liver fibrosis, which may be a promising therapeutic strategy for liver cirrhosis.


Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 278
Author(s):  
Alina Grama ◽  
Lucia Burac ◽  
Cornel Olimpiu Aldea ◽  
Bogdan Bulata ◽  
Dan Delean ◽  
...  

This study aimed to analyse vitamin D-binding protein (Gc-globulin) serum levels in acute liver failure (ALF) in children in relation to disease outcomes and correlations with other known markers used to evaluate the severity of ALF. Our study included 34 children (mean age 4.87 ± 5.30 years) with ALF of different causes (metabolic, 26.47%; autoimmune, 23.53%; toxic, 20.59%; infection, 17.65%; unknown, 11.76%) and 30 children without any liver injury (mean age 6.11 ± 4.26 years). The outcome was poor in 14 patients (41.18%), including one child with liver transplantation (2.94%). Serum Gc-globulin levels were significantly lower in ALF patients compared to the control group (151.57 ± 171.8 mg/L vs. 498.63 ± 252.50 mg/L; p < 0.000001), with an optimum cut-off of 163.5 mg/L (Area Under the Curve, AUC, 0.8921; sensitivity, 76.50%; specificity, 100%). Levels were also lower in patients with poor outcomes compared to survivors (59.34 ± 33.73 mg/L vs. 216.12 ± 199.69 mg/L; p < 0.0001), with an optimum cut-off 115 mg/L (AUC, 0.7642; sensitivity, 100%; specificity, 50%). Gc-globulin serum levels were variable according to ALF aetiology, i.e., lower in metabolic, infectious, or unknown causes compared to autoimmune and toxic causes. Gc-globulin serum levels were decreased in children with ALF and lower in those with poor outcomes compared with survivors. Gc-globulin serum levels were correlated with other known parameters used to evaluate the severity of ALF and could help to identify patients at high risk for poor outcomes.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Tariq Helal Ashour

The therapeutic efficacy of interleukin-22 (IL-22) on liver injury and hematological disturbances was studied in rat model of acute liver failure (ALF) induced by D-galactosamine/lipopolysaccharide (D-GalN/LPS). The following parameters were investigated: (1) survival rate, (2) serum levels of liver function enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)), total bilirubin (TBILI), and total albumen (ALB), (3) blood clotting tests (prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen level (FIB)) and white blood cells (WBCs), red blood cells (RBCs), and platelet counts, (4) hepatic levels of tumor necrosis factor-α(TNF-α) and cyclooxygenase-2 (COX-2), and (5) liver histopathology. After 48 hours of D-GalN/LPS, the rats exhibited 20% mortality, significant increases in AST, ALT, ALP, TBILI, PT, and aPTT, TNF-α, and COX-2 and significant decreases in FIB, WBCs, and RBCs. By contrast, therapy with IL-22 prevented the lethal effect of D-GalN/LPS by 100% and efficiently alleviated all the biochemical and hematological abnormalities that were observed in ALF untreated group. Furthermore, IL-22 treatment decreased the hepatic contents of TNF-αand COX-2. The histopathological findings also supported the hepatoprotective effect of IL-22. Taken together, therapy with IL-22 can represent a promising therapeutic tool against liver injury and its associated hemostasis disturbances.


2000 ◽  
Vol 31 (5) ◽  
pp. 557-561 ◽  
Author(s):  
John Tung ◽  
Nedim Hadzic ◽  
Mark Layton ◽  
Alastair J. Baker ◽  
Anil Dhawan ◽  
...  

2012 ◽  
Vol 20 (21) ◽  
pp. 1961
Author(s):  
Yang Zhang ◽  
Xiao-Yu Hu ◽  
Jian-Xing Luo ◽  
Guo Chen ◽  
Shu-Di Gao

Author(s):  
E. V. Migunova ◽  
M. Sh. Khubutiya ◽  
N. E. Kudryashova ◽  
O. G. Sinyakova ◽  
G. A. Berdnikov ◽  
...  

Objective. The study objective was to assess the scintigraphy potential in the evaluation of portal hypertension and the severity of liver damage in diffuse diseases and after liver transplantation.Material and methods. The study enrolled 325 patients suffering from hepatitis and liver cirrhosis of various etiology and severity, including those after liver transplantation, namely, the patients with hepatitis (n=96), patients with liver cirrhosis of Child–Pugh class A (n=24), class B (n=87), and class C (n=118); 11 more healthy volunteers without clinical and laboratory signs of diffuse liver disease were enrolled as controls. The assessment of liver reticuloendothelial system was performed by scintigraphy with (99m)Tc-phytate colloid in a static planar mode and "whole body" mode by SPECT (Infinia II, GE).Results. In contrast to the control group, significant radionuclide signs of hepatosplenomegaly were revealed with the predominant functional activity of the left lobe; the liver function was found impaired that correlated with the cirrhosis severity evaluated according to the Child–Pugh Сlassification. The analysis of scintigraphy quantitative parameters showed that the most informative of them were the intensity of radiopharmaceutical accumulation in the spleen (S%) and in bone marrow (Вm%), and the radiopharmaceutical uptake by the reticuloendothelial cells of the liver and spleen in percentage from the administered activity (Lwb%, Swb%). Depending on the cirrhosis severity assessed by the Child–Pugh Score, the changes in quantitative parameters were accompanied by a progressive enlargement of the spleen, liver left lobe, the increase of (99m)Tc-phytate uptake by the bone marrow with a decreased radiopharmaceutical uptake by the liver. The study results showed that among the Child–Pugh class C patients, the impairment of liver reticuloendothelial function was more pronounced in the patients with cirrhosis of viral and mixed etiology, when compared to those with alcoholic cirrhosis.Conclusion. The paper has identified the most informative parameters characterizing portal hypertension and the reticuloendothelial function for all Child–Pugh defined classes of cirrhosis. These parameters include the increase of (99m) Tc-phytate accumulation in the spleen (S%) and bone marrow (Bm%); the liver and spleen uptake of the radiopharmaceutical in percentage from the administered activity (Lwb%, Swb%). The calculation of the remaining parameters is necessary for a detailed description of the organ function and for the assessment of the portal hypertension severity in repeated studies.Summary. Criteria for the objective assessment of reticuloendothelial function and portal hypertension in diffuse liver diseases, including after liver transplantation, have been developed. Contrary to the control group, in patients with diffuse liver diseases, the radionuclide signs of hepatosplenomegaly (or a decreased liver size) with a predominant functional activity of the left lobe were identified, as were the changes in the quantitative parameters of the radiopharmaceutical uptake by the liver (Lwb%), including the radiopharmaceutical accumulation in the liver left lobe (Ll%), spleen (Swb%), bone marrow (Bm%), and the liver-to-spleen area ratio (Lar/Sar). The informative and reliable (p<0.05) parameters of the function Lwb%, S%, Swb% and Bm% correlating with the cirrhosis classes assessed by Child–Pugh were identified. The radionuclide method, being highly reproducible one, can be recommended for an objective assessment of liver function and the detection of portal hypertension in hepatitis and cirrhosis, as well as for post-transplant monitoring of the liver function to prevent complications in the early and late postoperative periods.


2019 ◽  
Vol 5 (6) ◽  
pp. 204-207
Author(s):  
Dr. Mohini Singh ◽  
◽  
Dr. Srilakshmi Sathiyaseelan ◽  
Devarasetty Shashank ◽  
Dr. S.R. Ramakrishnan ◽  
...  

Acute liver failure (ALF) is a condition with rapid deterioration of liver function resulting in hepatic encephalopathy and/or coagulopathy in patients with previously normal liver. Acute liver failure (ALF) is an uncommon condition associated with high morbidity and mortality. The prognosis is poor for untreated cases of Acute liver failure, so early recognition and management of patients with acute liver failure is crucial. A cause for acute liver failure can be identified in 60 to 80 percent of patients. Identifying the underlying cause of the liver failure is important because it influences the approach to management and provides prognostic information. Aims and Objectives: The aim of our study is to identify the clinical features, etiology and outcome of acute liver failure in a tertiary care hospital. Materials and Methods: This study is an observational study where patients with Acute Liver Failure admitted in ICU in our institution after meeting the diagnostic criteria for Acute liver failure were included in the study. Details of history, relevant symptoms and baseline investigations included, complete blood count, blood glucose, renal function test, serum electrolytes, liver function test (LFT), prothrombin time, international normalized ratio (INR), lactate dehydrogenase (LDH), creatine kinase (CK)], arterial blood gas analysis, arterial lactate, arterial ammonia, amylase and lipase level and pregnancy test (if female) and ultrasonography (USG) abdomen were recorded, MRI brain and other investigations relevant to the admission diagnosis, co morbidities and aetiology if needed were recorded. All the patients received standard supportive treatment for ALF. Results: In this study of 57 patients, majority of the patients were from the age group 41 to 50 years (17 patients) and 31 to 40 years (13 patients). 36 patients were male and 21 patients were females. Jaundice and encephalopathy was observed in all 57 (100%) patients, 24 (42%) patients had INR >2.5, 27 (47%) patients had serum creatinine >1.2 mg/dl and 18 (31.5%) patients had serum ammonia levels >100 micromol/L. The lowest value for serum aminotranferase was observed in infections (other than viral hepatitis) and maximum value was observed in drugs leading to ALF.In 20 (35%) patients viral hepatitis was the cause for ALD, followed by drugs and toxins which was the cause of ALD in 18 (31.5%) patients. Infections other viral hepatitis as the aetiology for ALF was observed in 16 (28%) of patients. Ischemic hepatitis was observed in 1 and Wilson’s disease was noted in 2 patients. Total 6 (10.5%) patients out of 57 patients had died, 4 patients with hepatitis B infection, 1 patient with paracetamol over dosage and 1 patient with dengue fever had died. Conclusion: Viral hepatitis and drugs are the commonest cause for acute liver failure. The aetiology of ALF varies significantly worldwide. Determining the etiology of acute liver failure requires a combination of detailed history taking and investigations. A broad evaluation is required to identify a cause of the acute liver failure, as the prognosis is poor in untreated cases of acute liver failure, so early recognition and management of patients with acute liver failure is crucial.


2018 ◽  
Vol 33 (2) ◽  
pp. 2514-2525 ◽  
Author(s):  
Yang Liu ◽  
Haozhen Ren ◽  
Jinglin Wang ◽  
Faji Yang ◽  
Jun Li ◽  
...  

2020 ◽  
Author(s):  
qiong Ning ◽  
xiangxin li ◽  
Xiangdong Jian ◽  
Xiaopeng He

Abstract To study the mechanism of Tim-3 on immune escape in benzene-induced acute myeloid leukemia (AML), to provide potential targets of clinical monitoring and intervention of hematological toxicity in benzene-induced AML . C3H/He mice were randomly divided into control group and experimental group. Serum levels of IL-12 in the experimental group were significantly lower than that in the control group. Serum levels of TGF-β1 in the experimental group were significantly higher than that in the control group( p <0.05). The proportion of Tim-3 positive CD14 + monocytes of bone marrow and spleen in the experimental group were both significantly higher than that in the control group ( p <0.05) by Flow cytometry (FCM). Compared with the control group, the expression of Tim-3 on (M1+M2) macrophages of bone marrow in the experimental group significantly increased by immunofluorescence assay. The expression of type M2 macrophages in (M1+M2) macrophages of bone marrow and spleen tissues in the experimental group were both higher than that in the control group. The expression levels of p-PI3K, p-AKT and p-mTOR in the experimental group were all significantly higher than that in the control group. Tim-3 was highly expressed in macrophages in benzene-induced AML. It promoted the activation of PI3K/AKT/mTOR signaling pathway, stimulated the secretion of anti-inflammatory cytokines, and inhibited the secretion of pro-inflammatory cytokines. High expression of Tim-3 changed the phenotype and function of macrophages by promoting the macrophages polarization, thus inducing negative immune response in the tumor microenvironment and tumor immune escape.


Author(s):  
James Y. Findlay ◽  
Eelco F. M. Wijdicks

Acute liver failure (ALF) is an uncommon condition in which an acute insult results in a rapid deterioration of liver function, encephalopathy, and coagulopathy in the absence of prior underlying liver disease. It is differentiated from rapid deterioration in the setting of underlying liver disease (acute on chronic liver failure) and from the gradual deterioration in liver function that can occur in chronic liver failure.


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