scholarly journals Enhanced therapeutic effects of umbilical cord mesenchymal stem cells after prolonged treatment for HBV-related liver failure and liver cirrhosis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yifan Jia ◽  
Xin Shu ◽  
Xiaoan Yang ◽  
Haixia Sun ◽  
Huijuan Cao ◽  
...  
2020 ◽  
Author(s):  
Yifan Jia ◽  
Xin Shu ◽  
Xiaoan Yang ◽  
Haixia sun ◽  
Huijuan Cao ◽  
...  

Abstract Background: This study aimed to investigate the therapeutic effect of umbilical cord mesenchymal stem cells (UCMSCs) on HBV-related liver failure and liver cirrhosis and to compare the different efficacies of UCMSCs after different treatment courses.Methods: This was an observational study that retrospectively considered a three-year period during which 513 patients who received stem cell infusion met the criteria of hepatic failure and liver cirrhosis were identified from databases of the Third Affiliated Hospital of Sun Yat-sen University. Eligible patients were categorized into the liver failure group and liver cirrhosis group. The two groups were divided into different subgroups according to the times of stem cell therapy. In the liver failure group, group A received more than 4 weeks and group B received less than 4 weeks. In the liver cirrhosis group, patients who received more than 4 weeks of stem cell therapy belonged to group C, and group D received less than 4 weeks. The patients were followed up for 24 weeks. The demographics, clinical characteristics, biochemical factors, and MELD scores were recorded and compared among different groups.Results: A total of 64 patients met the criteria of liver failure, and 59 patients met the criteria of liver cirrhosis. After UCMSC treatments, the levels of ALT, AST, and TBIL at all postbaseline time points were significantly lower than those at baseline in the liver failure group and liver cirrhosis group; the PTA and MELD scores only gradually improved in the liver failure group. Four weeks after UCMSC treatment, patients with prolonged treatment with UCMSCs had higher TBIL decline levels than patients who terminated treatment with UCMSCs. After more than 4 weeks of UCMSC treatment, there was no statistically significant difference in the levels of change for ALT, AST, TBIL, PTA value and the MELD score between patients with liver failure with prolonged treatment with UCMSCs and patients with liver cirrhosis with prolonged treatment with UCMSCs at all observation weeks. However, the median decline and cumulative decline in the TBIL level of patients with liver failure with a standard 4-week treatment course were higher than those of patients with liver cirrhosis with a standard 4-week treatment course.Conclusion: Peripheral infusion of UCMSCs showed good therapeutic effects for HBV-related liver failure and liver cirrhosis. Prolonging the treatment course can increase the curative effect of UCMSCs for end-stage liver disease, especially for patients with cirrhosis.


2020 ◽  
Author(s):  
Yifan Jia ◽  
Xin Shu ◽  
Xiaoan Yang ◽  
Haixia sun ◽  
Huijuan Cao ◽  
...  

Abstract Background: This study aimed to investigate the therapeutic effect of umbilical cord mesenchymal stem cells (UCMSCs) on HBV-related liver failure and liver cirrhosis and to compare the different efficacies of UCMSCs after different treatment courses. Methods: This was an observational study that retrospectively considered a three-year period during which 513 patients who received stem cell infusion met the criteria of hepatic failure and liver cirrhosis were identified from databases of the Third Affiliated Hospital of Sun Yat-sen University. Eligible patients were categorized into the liver failure group and liver cirrhosis group. The two groups were divided into different subgroups according to the times of stem cell therapy. In the liver failure group, group A received more than 4 weeks and group B received less than 4 weeks. In the liver cirrhosis group, patients who received more than 4 weeks of stem cell therapy belonged to group C, and group D received less than 4 weeks. The patients were followed up for 24 weeks. The demographics, clinical characteristics, biochemical factors, and MELD scores were recorded and compared among different groups. Results: A total of 64 patients met the criteria of liver failure, and 59 patients met the criteria of liver cirrhosis. After UCMSC treatments, the levels of ALT, AST, and TBIL at all postbaseline time points were significantly lower than those at baseline in the liver failure group and liver cirrhosis group; the PTA and MELD scores only gradually improved in the liver failure group. Four weeks after UCMSC treatment, patients with prolonged treatment with UCMSCs had higher TBIL decline levels than patients who terminated treatment with UCMSCs. After more than 4 weeks of UCMSC treatment, there was no statistically significant difference in the levels of change for ALT, AST, TBIL, PTA value and the MELD score between patients with liver failure with prolonged treatment with UCMSCs and patients with liver cirrhosis with prolonged treatment with UCMSCs at all observation weeks. However, the median decline and cumulative decline in the TBIL level of patients with liver failure with a standard 4-week treatment course were higher than those of patients with liver cirrhosis with a standard 4-week treatment course. Conclusion: Peripheral infusion of UCMSCs showed good therapeutic effects for HBV-related liver failure and liver cirrhosis. Prolonging the treatment course can increase the curative effect of UCMSCs for end-stage liver disease, especially for patients with cirrhosis.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ka Zhang ◽  
Haixia Sun ◽  
Huijuan Cao ◽  
Yifan Jia ◽  
Xin Shu ◽  
...  

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.


2021 ◽  
Author(s):  
Ka Zhang ◽  
Haixia Sun ◽  
Huijuan Cao ◽  
Yifan Jia ◽  
Xin Shu ◽  
...  

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.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yongting Zhang ◽  
Yuwen Li ◽  
Wenting Li ◽  
Jie Cai ◽  
Ming Yue ◽  
...  

Recent studies have described beneficial effects of an infusion of mesenchymal stem cells (MSCs) derived from Wharton’s jelly tissue, for the treatment of acute liver failure (ALF). However, data on the therapeutic potential of culture-expanded MSCs are lacking. We examined the therapeutic potential of passage five (P5) and ten (P10) human umbilical cord- (hUC-) MSCs via their transplantation into Sprague-Dawley (SD) rats with D-galactosamine (D-GalN) and LPS-induced acute liver failure (ALF). SD rats were randomly divided into three groups: control group, P5 hUC-MSCs group, and P10 hUC-MSCs group. After transplantation, P5 hUC-MSCs provided a significant survival benefit. The analysis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) levels showed that transplantation with P5 hUC-MSCs was more effective than treatment with P10 hUC-MSCs. P5 hUC-MSCs also successfully downregulated the hepatic activity index (HAI) scores. Compared to P10 hUC-MSCs in vivo, P5 hUC-MSCs significantly enhanced the regeneration and inhibited the apoptosis of hepatocytes. CM-Dil-labeled hUC-MSCs were found to engraft within the recipient liver, whereas the homing of cells to the recipient liver in the P10 hUC-MSCs group was less effective compared to the P5 hUC-MSCs group. Previous studies have shown that the concentration of hepatocyte growth factor (HGF) in the injured liver was significantly increased. HGF is commonly known as the ligand of c-Met. The level of c-Met in hUC-MSCs as detected by Western blotting indicated that at a higher passage number, there is a decrease in c-Met. These data suggest that direct transplantation of P5 hUC-MSCs can more efficiently home to an injured liver. Subsequently, the P5 hUC-MSCs can rescue ALF and repopulate the livers of rats through the stimulation of endogenous liver regeneration and inhibition of hepatocellular apoptosis for compensated liver function, which is dependent on the higher level of c-Met than P10 hUC-MSCs.


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