scholarly journals Transplantation of Autologous Mesenchymal Stem Cells for End-Stage Liver Cirrhosis: A Meta-Analysis Based on Seven Controlled Trials

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Xiang-Rui Ma ◽  
Ya-Ling Tang ◽  
Ming Xuan ◽  
Zheng Chang ◽  
Xiao-Yi Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Liver Function ◽  
Serum Albumin ◽  
Total Bilirubin ◽  
Meta Analysis ◽  
Meld Score ◽  
End Stage

Background. The bone marrow-derived mesenchymal stem cells (BM-MSCs) have demonstrated great potential as regenerative medicine in different therapeutic applications. This study aims to pool previous controlled clinical trials to make an update assessment of the effectiveness of BM-MSC transplantation on end-stage liver cirrhosis.Methods. Relevant studies published between January 1990 and June 2014 were searched among Pubmed, Embase, and ClinicalTrial.gov. A meta-analysis was performed to assess the effect of BM-MSCs on liver function indicators, including Models of End-Stage Liver Disease (MELD) score, serum albumin (g/L), total bilirubin (mg/dl), Prothrombin concentration (%), and alanine aminotransferase (ALT) (U/L).Results. BM-MSCs therapy could significantly improve liver function in patients with end-stage liver cirrhosis, in terms of MELD score, serum albumin, total bilirubin, and prothrombin concentration, at least during the half year after transplantation.Conclusions. Due to BM-MSCs’ immunomodulatory functions and the potential to differentiate into hepatocytes, they are a promising therapeutic agent to liver cirrhosis. Considering currently available evidence, this therapy is relatively safe and effective in improving liver function. However, how different variables should be controlled to optimize the therapeutic effect is still not clear. Thus, future mechanism studies and clinical trials are required for this optimization.

A Pilot Study To Evaluate the Safety, Efficacy and Effects on Liver Function of Granulocyte Colony-Stimulating Factor To Mobilize Hematopoietic Stem Cells in Patients with Liver Cirrhosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1698-1698
Author(s):  
Alessandro Isidori ◽  
Lucia Catani ◽  
Simona Talarico ◽  
Stefania Lorenzini ◽  
Elisabetta Loggi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Cirrhosis ◽  
Liver Function ◽  
Hematopoietic Stem Cells ◽  
Meld Score ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Chronic Liver Damage ◽  
Hematopoietic Stem ◽  
Stimulating Factor

Abstract In animal models hematopoietic stem cells (HSCs) and the hematopoietic cytokine granulocyte colony-stimulating factor (G-CSF) contribute to tissue regeneration after acute or chronic liver damage. In this study, we assessed whether: 1) G-CSF can be safely administered to patients with liver cirrhosis to expand and mobilize HSCs into peripheral blood; 2) G-CSF treatment affects residual liver function. Eighteen patients with a Child-Turcotte-Pugh (CTP) score < 10 and a Mayo Model for End Stage Liver Disease (MELD) score < 20 were considered eligible for the study. Increasing doses of G-CSF were administered subcutaneously for 7 consecutive days to 5 cohorts of 3 patients each, starting from 2.2 μg/kg/daily, until the achievement of the maximum-tolerated dose and/or the successful mobilization of ≥10 CD34+ cells/μl in at least 2/3 patients. G-CSF mobilizing dose was found at 15 μg/kg/day. Four additional patients were treated with the mobilizing G-CSF dose. All of them showed a successful mobilization of HSCs with a median peak value of CD34+ and CD133+ cells of 27.1(±15.5) and 15.2 (±5.1)/μl, respectively. Circulating HSCs were then collected by single volume leukapheresis and a median of 1.4(±0.73)x106 CD34+ HSCs/kg body weight were cryopreserved. G-CSF treatment induced a significant increase of hepatocyte growth factor serum level. When we analyzed stem cell subsets, we found significant mobilization of early hematopoietic (CD34+/CD38−) and endothelial (CD34+/KDR+, CD133+/KDR+) progenitors as well as CD34+/CXCR4+ cells. No severe adverse events were observed at any dosage or during leukapheresis. According to CTP and MELD score, no significant modification of liver function was observed during the treatment period and follow up (median=198 days) in both mobilizing and non-mobilizing patients. Nevertheless, in all treated patients a significant reduction of alpha-fetoprotein values was observed (p<0.001). In conclusion, the administration of G-CSF to patients with liver cirrhosis is safe, feasible and capable of mobilizing HSCs at the dosage of 15 μg/kg/day. Our study represents the first step for evaluating the role of G-CSF and mobilized HSCs to improve liver function in patients with liver cirrhosis.

scholarly journals Umbilical Cord Blood-Derived Mesenchymal Stem Cells Transplantation Decreases Incidence of Liver Cancer in End-Stage Liver Disease Patients: A Retrospective Analysis Over 5 Years

2021 ◽  
Author(s):  
Le Luo ◽  
Cun-You Lai ◽  
Tian-Hang Feng ◽  
Yu-Tong Yao ◽  
Hua Xue ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Liver Disease ◽  
Liver Cancer ◽  
Umbilical Cord Blood ◽  
End Stage Liver Disease ◽  
Liver Cancers ◽  
End Stage

Abstract Background: End-stage liver disease (ESLD) is the final stage of a liver disease, which is characterized by liver cirrhosis. ESLD largely increases possibility of liver cancers in the world. The stem cell transplantation has become an emerging therapy to treat various liver diseases including ESLD, while whether it causes liver cancer remains unclear. The study aims to analysis the long-term therapeutic effect of umbilical cord blood-derived mesenchymal stem cells (UC-MSCs) transplantation in ESLD patients. Patients and Methods: 50 ELSD patients of non-UC-MSCs transplantation and 45 ELSD patients of UC-MSCs transplantation were retrospectively analyzed. The clinical outcomes in clinical and biochemical data, complications, and quality of life were recorded at 3, 6, 12, 36, and 60 months. Results: It was found that the incidence of liver cancer was much lower in ESLD patients with UC-MSCs transplantation than in ESLD patients without UC-MSCs transplantation (12% VS 2.2%). The survival percentage was improved by treatment with UC-MSCs transplantation compared with non-UC-MSCs transplantation in ESLD patients during the five years follow-up. The inflammation and fibrosis scores were decreased in the ESLD patients with UC-MSCs transplantation. The liver cirrhosis was largely improved, and Child-Pugh scores were decreased. Conclusions: UC-MSCs transplantation is able to decrease the risks of liver cancers in ELSD patients. The reduction of liver cancer incidence might be related to decrease of inflammation by UC-MSCs transplantation. More efforts should be investigated towards increasing the number of patients and follow-up time to further verify the therapeutic benefits of UC-MSCs translations in treating liver cancers.

Single-Cell Profiles and Clinically Useful Properties of Human Mesenchymal Stem Cells of Adipose and Bone Marrow Origin

2019 ◽  
Vol 47 (7) ◽  
pp. 1722-1733 ◽  
Author(s):  
Wenyan Zhou ◽  
Junxin Lin ◽  
Kun Zhao ◽  
Kaixiu Jin ◽  
Qiulin He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Single Cell ◽  
Clinical Outcomes ◽  
Clinical Application ◽  
Meta Analysis ◽  
Osteoarthritis Treatment ◽  
Cell Source

Background: Mesenchymal stem cells (MSCs) can be isolated from various tissues and can present themselves as a promising cell source for cell-based therapies. Although adipose- and bone marrow–derived mesenchymal stem cells have already been used in a considerable number of clinical trials for osteoarthritis treatment, systematic analyses from single- to bulk-cell resolution as well as clinical outcomes of these 2 MSCs are still insufficient. Purpose: To explore the characteristics and differences of adipose-derived stem cells (ADSCs) and bone marrow MSCs (BMSCs) at single- and bulk-cell levels, to study the clinical outcomes of these 2 cells on the treatment of osteoarthritis, and to provide potential guidance on the more precise clinical application of these MSCs. Study Design: Controlled laboratory study and meta-analysis. Methods: Same donor–derived ADSCs and BMSCs were isolated and cultured. Single- and bulk-cell assays were used to identify the characteristics of these 2 cells. Meta-analysis of clinical trials was done to compare the clinical therapeutic effects in osteoarthritis treatment with ADSCs and BMSCs. Results: Single-cell RNA sequencing analysis showed that the population of ADSCs showed lower transcriptomic heterogeneity when compared with BMSCs. Additionally, as compared with BMSCs, ADSCs were less dependent on mitochondrial respiration for energy production. Furthermore, ADSCs had a lower expression level of human leukocyte antigen class I antigen and higher immunosuppression capacity when compared with the BMSC population. Meta-analysis of current clinical trials of osteoarthritis treatment with MSCs consistently showed that ADSCs are more stable than BMSCs in their therapeutic effect. Conclusion: These results provide basic biological insights into human ADSCs and BMSCs at the single-cell resolution. Findings indicated that ADSCs may be a more controllable stem cell source, may be more adaptable to surviving in the hypoxic articular cavity niche, and may exhibit superiority in regulating inflammation. Based on the meta-analysis results of the different characteristics of ADSCs and BMSCs, ADSCs were implicated as being a better cell source for osteoarthritis treatment. Clinical Relevance: These results guide a more precise clinical application of adipose and bone marrow mesenchymal stem cells.

scholarly journals Cellular Therapeutics for Heart Failure: Focus on Mesenchymal Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Amitabh C. Pandey ◽  
Jordan J. Lancaster ◽  
David T. Harris ◽  
Steven Goldman ◽  
Elizabeth Juneman
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Cellular Level ◽  
Paracrine Signaling ◽  
End Stage Heart Failure ◽  
End Stage ◽  
Pharmacologic Agents ◽  
Cellular Therapeutics

Resulting from a various etiologies, the most notable remains ischemia; heart failure (HF) manifests as the common end pathway of many cardiovascular processes and remains among the top causes for hospitalization and a major cause of morbidity and mortality worldwide. Current pharmacologic treatment for HF utilizes pharmacologic agents to control symptoms and slow further deterioration; however, on a cellular level, in a patient with progressive disease, fibrosis and cardiac remodeling can continue leading to end-stage heart failure. Cellular therapeutics have risen as the new hope for an improvement in the treatment of HF. Mesenchymal stem cells (MSCs) have gained popularity given their propensity of promoting endogenous cellular repair of a myriad of disease processes via paracrine signaling through expression of various cytokines, chemokines, and adhesion molecules resulting in activation of signal transduction pathways. While the exact mechanism remains to be completely elucidated, this remains the primary mechanism identified to date. Recently, MSCs have been incorporated as the central focus in clinical trials investigating the role how MSCs can play in the treatment of HF. In this review, we focus on the characteristics of MSCs that give them a distinct edge as cellular therapeutics and present results of clinical trials investigating MSCs in the setting of ischemic HF.

scholarly journals Doppler ultrasound in liver cirrhosis: correlation of hepatic artery and portal vein measurements with model for end-stage liver disease score in Egypt

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Ahmed Abdelrahman Mohamed Baz ◽  
Rana Magdy Mohamed ◽  
Khaled Helmy El-kaffas
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Portal Vein ◽  
Hepatic Artery ◽  
Meld Score ◽  
Hepatic Decompensation ◽  
End Stage Liver Disease ◽  
Cirrhotic Patients ◽  
Us Findings ◽  
End Stage

Abstract Background Liver cirrhosis is a multi-etiological entity that alters the hepatic functions and vascularity by varying grades. Hereby, a cross-sectional study enrolling 100 cirrhotic patients (51 males and 49 females), who were diagnosed clinically and assessed by model for end-stage liver disease (MELD) score, then correlated to the hepatic Doppler parameters and ultrasound (US) findings of hepatic decompensation like ascites and splenomegaly. Results By Doppler and US, splenomegaly was evident in 49% of patients, while ascites was present in 44% of them. Increased hepatic artery velocity (HAV) was found in70% of cases, while 59% showed reduced portal vein velocity (PVV). There was a statistically significant correlation between HAV and MELD score (ρ = 0.000), but no significant correlation with either hepatic artery resistivity index (HARI) (ρ = 0.675) or PVV (ρ =0.266). Moreover, HAV had been correlated to splenomegaly (ρ = 0.000), whereas HARI (ρ = 0.137) and PVV (ρ = 0.241) did not significantly correlate. Also, ascites had correlated significantly to MELD score and HAV (ρ = 0.000), but neither HARI (ρ = 0.607) nor PVV (ρ = 0.143) was significantly correlated. Our results showed that HAV > 145 cm/s could confidently predict a high MELD score with 62.50% and 97.62 % sensitivity and specificity. Conclusion Doppler parameters of hepatic vessels (specifically HAV) in addition to the US findings of hepatic decompensation proved to be a non-invasive and cost-effective imaging tool for severity assessment in cirrhotic patients (scored by MELD); they could be used as additional prognostic parameters for improving the available treatment options and outcomes.

scholarly journals Mesenchymal stem cells and oncolytic viruses: joining forces against cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001684
Author(s):  
Rafael Moreno
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Immune System ◽  
Oncolytic Viruses ◽  
Immunogenic Cell Death ◽  
The Past ◽  
Physical Barriers ◽  
Immunogenic Properties ◽  
New Strategies

The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving approval for some indications. Recently, OVs have also gathered interest as candidates to use in combination with immunotherapies for cancer due to their immunogenic properties, which include immunogenic cell death and the possibility to carry therapeutic transgenes in their genomes. OVs transform non-immunogenic ‘cold’ tumors into inflamed immunogenic ‘hot’ tumors, where immunotherapies show the highest efficacy. However, in monotherapy or in combination with immunotherapy, OVs face numerous challenges that limit their successful application, in particular upon systemic administration, such as liver sequestration, neutralizing interactions in blood, physical barriers to infection, and fast clearance by the immune system. In this regard, the use of mesenchymal stem cells (MSCs) as cells carrier for OV delivery addresses many of these obstacles acting as virus carriers and factories, expressing additional transgenes, and modulating the immune system. Here, I review the current progress of OVs-loaded MSCs in cancer, focusing on their interaction with the immune system, and discuss new strategies to improve their therapeutic efficacy.

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