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

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 30 ◽  
pp. 096368972198926
Author(s):  
Liyi Huang ◽  
Chenying Fu ◽  
Feng Xiong ◽  
Chengqi He ◽  
Quan Wei

Traumatic spinal cord injury (SCI) results in direct and indirect damage to neural tissues, which results in motor and sensory dysfunction, dystonia, and pathological reflex that ultimately lead to paraplegia or tetraplegia. A loss of cells, axon regeneration failure, and time-sensitive pathophysiology make tissue repair difficult. Despite various medical developments, there are currently no effective regenerative treatments. Stem cell therapy is a promising treatment for SCI due to its multiple targets and reactivity benefits. The present review focuses on SCI stem cell therapy, including bone marrow mesenchymal stem cells, umbilical mesenchymal stem cells, adipose-derived mesenchymal stem cells, neural stem cells, neural progenitor cells, embryonic stem cells, induced pluripotent stem cells, and extracellular vesicles. Each cell type targets certain features of SCI pathology and shows therapeutic effects via cell replacement, nutritional support, scaffolds, and immunomodulation mechanisms. However, many preclinical studies and a growing number of clinical trials found that single-cell treatments had only limited benefits for SCI. SCI damage is multifaceted, and there is a growing consensus that a combined treatment is needed.


2009 ◽  
Vol 35 (2) ◽  
pp. 85-93 ◽  
Author(s):  
L. Vija ◽  
D. Farge ◽  
J.-F. Gautier ◽  
P. Vexiau ◽  
C. Dumitrache ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Gee-Hye Kim ◽  
Yun Kyung Bae ◽  
Ji Hye Kwon ◽  
Miyeon Kim ◽  
Soo Jin Choi ◽  
...  

Autophagy plays a critical role in stem cell maintenance and is related to cell growth and cellular senescence. It is important to find a quality-control marker for predicting senescent cells. This study verified that CD47 could be a candidate to select efficient mesenchymal stem cells (MSCs) to enhance the therapeutic effects of stem cell therapy by analyzing the antibody surface array. CD47 expression was significantly decreased during the expansion of MSCs in vitro ( p < 0.01 ), with decreased CD47 expression correlated with accelerated senescence phenotype, which affected cell growth. UCB-MSCs transfected with CD47 siRNA significantly triggered the downregulation of pRB and upregulation of pp38, which are senescence-related markers. Additionally, autophagy-related markers, ATG5, ATG12, Beclin1, and LC3B, revealed significant downregulation with CD47 siRNA transfection. Furthermore, autophagy flux following treatment with an autophagy inducer, rapamycin, has shown that CD47 is a key player in autophagy and senescence to maintain and regulate the growth of MSCs, suggesting that CD47 may be a critical key marker for the selection of effective stem cells in cell therapy.


2019 ◽  
Vol 20 (6) ◽  
pp. 1420 ◽  
Author(s):  
Bernhard Wernly ◽  
Moritz Mirna ◽  
Richard Rezar ◽  
Christine Prodinger ◽  
Christian Jung ◽  
...  

Although reperfusion therapy has improved outcomes, acute myocardial infarction (AMI) is still associated with both significant mortality and morbidity. Once irreversible myocardial cell death due to ischemia and reperfusion sets in, scarring leads to reduction in left ventricular function and subsequent heart failure. Regenerative cardiovascular medicine experienced a boost in the early 2000s when regenerative effects of bone marrow stem cells in a murine model of AMI were described. Translation from an animal model to stem cell application in a clinical setting was rapid and the first large trials in humans suffering from AMI were conducted. However, high initial hopes were early shattered by inconsistent results of randomized clinical trials in patients suffering from AMI treated with stem cells. Hence, we provide an overview of both basic science and clinical trials carried out in regenerative cardiovascular therapies. Possible pitfalls in specific cell processing techniques and trial design are discussed as these factors influence both basic science and clinical outcomes. We address possible solutions. Alternative mechanisms and explanations for effects seen in both basic science and some clinical trials are discussed here, with special emphasis on paracrine mechanisms via growth factors, exosomes, and microRNAs. Based on these findings, we propose an outlook in which stem cell therapy, or therapeutic effects associated with stem cell therapy, such as paracrine mechanisms, might play an important role in the future. Optimizing stem cell processing and a better understanding of paracrine signaling as well as its effect on cardioprotection and remodeling after AMI might improve not only AMI research, but also our patients’ outcomes.


2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Jeanne AdiwinataPawitan

Background. Alternative approaches to transplantation for liver failure are needed. One of the alternative approaches is stem cell therapy. However, stem cell therapy in liver failure is not standardized yet, as every centre have their own methods. This systematic review is aimed at compiling and analyzing the various studies that use stem cells to treat liver failure, to get an insight into potential protocols in terms of safety and efficacy by comparing them to controls. Methods. This systematic review was done according to PRISMA guidelines and submitted for registration in PROSPERO (registration number CRD42018106119). All published studies in PubMed/MEDLINE and Cochrane Library, using key words: “human” and “stem cell” AND “liver failure” on 16th June 2018, without time restriction. In addition, relevant articles that are found during full-text search were added. Inclusion criteria included all original articles on stem cell use in humans with liver failure. Data collected included study type, treatment and control number, severity of disease, concomitant therapy, type and source of cells, passage of cells, dose, administration route, repeats, and interval between repeats, outcomes, and adverse events compared to controls. Data were analyzed descriptively to determine the possible causes of adverse reactions, and which protocols gave a satisfactory outcome, in terms of safety and efficacy. Results. There were 25 original articles, i.e., eight case studies and 17 studies with controls. Conclusion. Among the various adult stem cells that were used in human studies, MSCs from the bone marrow or umbilical cord performed better compared to other types of adult stem cells, though no study showed a complete and sustainable performance in the outcome measures. Intravenous (IV) route was equal to invasive route. Fresh or cryopreserved, and autologous or allogeneic MSCs were equally beneficial; and giving too many cells via intraportal or the hepatic artery might be counterproductive.


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