scholarly journals Human Menstrual Blood-derived Stem Cell Transplantation Suppresses Liver Injury in DDC-induced Chronic Cholestasis

Author(s):  
Ya Yang ◽  
Yanfei Chen ◽  
Yalei Zhao ◽  
Feiyang Ji ◽  
Lingjian Zhang ◽  
...  

Abstract Background: Cholestasis liver injury can lead to serious symptoms and prognoses in the clinic. Currently, an effective medical treatment is not available for cholestasis liver injury. Human menstrual blood-derived stem cells (MenSCs) have been considered an emerging treatment in various diseases. However, efficiency of MenSCs in cholestasis liver injury has been less investigated. Methods: C57/BL6 mice were fed with 3,5-diethoxycarbonyl-1,4- dihydroxychollidine (DDC) to induce chronic cholestasis liver injury model. DDC mice were injected with either phosphate buffer saline (PBS) or MenSCs at 2 and 4 weeks. Mice were sacrificed at 5 weeks. Serum and liver tissues were collected to test liver function and pathological changes. Proteomics and western blot were used to explore the related molecular mechanisms. Adeno-associated virus (AAV)9 infected mice were used for verifications of MenSC treatment target and related molecular mechanism. Results: We found that MenSCs could protect mice against DDC-induced cholestasis by improving impaired liver function and tissue damage. MenSCs markedly prolonged survival rate of mice, decreased the mice serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (DBIL) and total bilirubin (TBIL) levels as well as intrahepatic cholestasis, bile duct dilation and fibrosis. The results further indicated that MenSCs repaired DDC-induced tight junction (TJ) and bile transport function damage and inhibited COL1A1, α-SMA and TGF-β1 activation by upregulating liver β-catenin expression. MenSC transplantation could be an effective treatment method for cholestasis liver injury.

1985 ◽  
Vol 54 (03) ◽  
pp. 617-618 ◽  
Author(s):  
J C Kirchheimer ◽  
K Huber ◽  
P Polterauer ◽  
B R Binder

SummaryPlasma urokinase antigen levels were studied in 78 patients suffering from liver diseases. Blood was drawn before any specific medication was initiated. Impairment of liver function was comparable in all patients. In both groups of cirrhotic liver disease (alcoholic and non-alcoholic), normal levels of plasma urokinase antigen were found as compared to age-matched control groups. In both groups of patients with hepatomas (with or without a history of liver cirrhosis), however, significantly increased plasma urokinase antigen levels could be determined. These data indicate that an increase in plasma urokinase antigen might rather relate to malignant growth in liver disease than to impaired liver function.


2015 ◽  
pp. 93 ◽  
Author(s):  
Rajshekhar Chakraborty ◽  
Shiva Kumar Reddy Mukkamalla ◽  
Garfield Gutzmore ◽  
Hon Cheung Chan

2002 ◽  
Vol 13 (8) ◽  
pp. 847-849 ◽  
Author(s):  
Sebastian Bauer ◽  
Volker Hagen ◽  
Hermann J Pielken ◽  
Peter Bojko ◽  
Siegfried Seeber ◽  
...  

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yuli Y Kim ◽  
Greg Everson ◽  
Steve Helmke ◽  
Jessica Carducci ◽  
Andrew C Glatz ◽  
...  

Introduction: Currently there is no biomarker or test to accurately measure liver function in Fontan-associated liver disease. The dual cholate test (HepQuant SHUNT) is a noninvasive, flow-dependent assay measuring hepatic clearance of a bile acid, cholate, and may serve as a useful measure of liver function in the Fontan. We aim to measure cholate clearance in a cohort of Fontan patients and compare to normal controls. Methods: Single center, prospective pilot study of Fontan patients ≥ 18 years. Hepatic clearance of orally administered d4-cholate and intravenously administered 13C-cholate were measured in peripheral venous samples after 5, 20, 45, 60, and 90 minutes. Portal hepatic filtration rate (HFR), systemic HFR, shunt fraction (systemic HFR/portal HFR), and disease severity index (DSI) were calculated. Decline in HFRs and increase in shunt fraction or DSI is indicative of impaired liver function. Two-sided t-tests were used to compare values between Fontans and controls. Results: Twelve Fontan patients were enrolled (33% female, median age 29.9 [range 23.6 - 41.0] years). Median total bilirubin was 0.8 (range 0.3-2.1) mg/dL, AST 30.5 (range 16-55) U/L, ALT 32 (range 11-53) U/L, alkaline phosphatase 87 (range 42-191) U/L and platelets 177 (range 130-428) 10 3 /μL. Mean cardiac index was 3.0 ± 0.5 L/min/m 2 . Cholate clearance was lower in Fontans compared to controls (Figure). Mean portal HFR (mL/min/kg) in Fontans was lower than controls (15.1 ± 10.9 vs 29.1 ± 9.0; p<0.001) as well as systemic HFR (3.7 ± 1.3 vs 6.5 ± 1.5; p<0.001) whereas shunt fraction (%) was not (29.2 ± 11.4 vs 24.1 ± 7.5; p=NS). DSI was higher in Fontans compared to controls (19.4 ± 6.1 vs 9.2 ± 3.4; p<0.001). Conclusions: Fontan patients demonstrate reduced hepatic function compared to normal controls but there is considerable variability. Future studies using the dual cholate test will examine the relationship between liver and cardiac function, as well as risk of adverse clinical outcome, in the Fontan.


2019 ◽  
Vol 42 (1) ◽  
pp. 124-131
Author(s):  
Dorothea Strobach ◽  
Angelika Poppele ◽  
Hanna Mannell ◽  
Monika Andraschko ◽  
Susanne Schiek ◽  
...  

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