Mesenchymal Stem Cell Therapy in Decompensated Liver Cirrhosis: A Long-Term Follow-up Analysis of the Randomized Controlled Clinical Trial

Abstract

BackgroundMesenchymal stem cells (MSC) infusion was reported to improve liver function in patients with decompensated liver cirrhosis (DLC), however, whether the medication can improve outcome of these patients is poorly understand.MethodsThis prospective, open-labeled, randomized controlled study enrolled 219 patients with HBV-related DLC who were divided into control group (n=111) and umbilical cord-derived MSC (UC-MSC) treated group (n=108), then all of them received a follow-up check from October 2010 to October 2017. The treated patients received three times of UC-MSC infusions at 4-week intervals plus conventional treatment that was only used for control group. The overall survival rate and HCC-free survial rate were calculated as primary endpoints and the liver function and adverse events associated with the medication were also evaluated.ResultsDuring the follow-up check period from 13th to 75th months, there was a significantly higher overall survival rate in the treated group than the control group, while the difference of the hepatocellular carcinoma event-free survival rate between the treated and control groups was not observed during the 75-month follow-up. UC-MSC treatment markedly improved liver function, as indicated by the levels of serum albumin, prothrombin activity, cholinesterase, and total bilirubin during 48 weeks of follow-up. No significant side effects or treatment-related complications were observed in the UC-MSC group.ConclusionsTherapy of UC-MSC is not only well tolerated, but also significantly improves long-term survival rate, as well as the liver function in patients with DLC. UC-MSC medication, therefore, might present a novel therapeutic approach for the disease.

Therapeutic effect of autologous bone marrow cells injected into the liver under the guidance of B‑ultrasound in the treatment of HBV‑related decompensated liver cirrhosis

“…To the best of our knowledge, there is no specific drug for DLC and blocking the factors that cause further damage to liver cells is the basic treatment for post-hepatitis cirrhosis (12). Anti-HBV drugs, such as entecavir and tenofovir, can control the massive replication of HBV but cannot clear HBV, thus long-term antiviral treatment is required (21).…”

“…Stem cells are undifferentiated cells with the potential to differentiate into various cell types. The bone marrow contains hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells and other undifferentiated cells (12). Once these undifferentiated cells from the bone marrow are transplanted into the liver with hepatocyte injury, they can differentiate into hepatocytes in the liver microenvironment, or they can secrete certain cytokines to promote the repair of damaged hepatocytes and improve liver function (13).…”

Advance of Mesenchymal Stem Cells in Chronic End-Stage Liver Disease Control

“…In a clinical trial, only after patients were infused with UCMSCs for 13 months did survival rates increase [111]. However, further research is needed to determine the precise mechanism by which UCMSC treatment improves survival only after 13 months of treatment.…”

Exosomes Derived from Human Adipose Mesenchymal Stem Cells Ameliorate Hepatic Fibrosis by Regulating Choline Metabolism and PI3K/Akt/mTOR Pathway

“…Recently, mesenchymal stem cells (MSCs) as well as their derivates provide an alternative for patients with liver disorders. Various stem cells derived from human bone marrow (BMSCs), umbilical cord (UCSCs), and adipose tissue (ADSCs) has been utilized in the treatment of liver disease [10][11][12][13]. Both clinical and experimental evidences have shown that MSCs could e ciently protect hepatocytes by transdifferentiating into functional hepatocytes, secreting a wide range of immunosuppressive and trophic factors, and exosomes through autocrine or paracrine effects, leading to an anti brotic effect and promote liver regeneration [11,14].…”