Exploring the Efficacy and Safety of Mesenchymal Stem Cell Therapy for Liver Cirrhosis

Liver cirrhosis (LC) is a severe global health problem, contributing to an estimated two million deaths annually. LC results from chronic liver diseases such as hepatitis B and C, alcohol consumption, non-alcoholic fatty liver disease, and autoimmune liver disease. When these diseases progress unchecked, they lead to liver cirrhosis, characterized by inflammation and fibrosis. Most patients with LC die from complications due to a lack of effective treatments and poor patient compliance. While liver transplantation is effective, it is costly and comes with risks like immune rejection and recurrent infections. This has led to an urgent need for alternative treatments for LC.

Mesenchymal stem cells (MSCs) offer a promising alternative due to their ability to renew themselves and differentiate into various cell types. MSCs have gained attention for their potential to treat tissue-damaging diseases due to their low immunogenicity and ability to home to injury sites. Animal studies have shown MSCs to be safe and effective in treating LC, and clinical trials indicate improvements in liver function with no significant adverse effects. 

Lu et al.’s study aims to systematically evaluate the efficacy and safety of MSCs for treating liver cirrhosis through a meta-analysis of clinical trials.

As part of this study, the authors analyzed data from PubMed/Medline, Web of Science, EMBASE, and Cochrane Library up through May 2023. Researchers used the PICOS principle for literature screening and assessed the risk of bias. Data from each study’s outcome indicators, such as liver function and adverse events, were then extracted and analyzed using Review Manager 5.4.

Eleven clinical trials met the criteria for this analysis. The pooled data showed significant improvements in primary and secondary liver function indicators. Patients who received MSC infusions had higher albumin (ALB) levels at 2 weeks, 1 month, 3 months, and 6 months, and lower MELD scores at 1 month, 2 months, and 6 months compared to the control group. Hepatic arterial injections were particularly effective in improving these scores. Importantly, none of the studies reported severe adverse effects, indicating the safety of MSC therapy.

Key Findings and Recommendations

Considering the findings of this study, the authors provide a number of key findings and recommendations, including:

• Duration of MSC Therapy: The study found that prolonging MSC treatment enhances its effectiveness in end-stage liver disease, improving symptoms such as appetite loss, mental depression, and jaundice. 
• Types of MSCs: MSCs can be derived from various tissues, and their effectiveness may vary. Most studies evaluated used bone marrow-derived MSCs (BM-MSCs), which have shown superior therapeutic effects compared to umbilical cord-derived MSCs (UC-MSCs). However, more research is needed to determine the best type of MSC for treating LC.
• Routes of Administration: Different transplantation methods can impact the efficacy of MSC therapy. The hepatic artery route was found to be the most effective, likely due to better MSC homing to the liver. However, this method has clinical limitations such as high surgical risk. Intravenous administration, while safer, was less effective. The authors call for further research to optimize the administration route.
• Secondary Indicators: While primary indicators like MELD score and ALB levels showed significant improvements, secondary indicators such as ALT, AST, TBIL, and INR did not show significant differences between the MSC and control groups. The authors believe this could be due to variability in disease cause, patient population, and follow-up duration.
• Complications and Prognosis: MSC therapy also showed potential in reducing LC complications, such as portal hypertension and ascites, and decreasing mortality and hepatocellular carcinoma (HCC) incidence. However, more clinical trials are needed to confirm these findings and assess the long-term prognosis of MSC therapy in LC.

Lu et al. conclude that mesenchymal stem cell therapy is a safe and effective treatment for liver cirrhosis, significantly improving liver function without severe adverse effects. However, to fully realize the potential of MSC therapy, a standardized treatment protocol is needed. This includes optimizing the timing, dosage, frequency, and administration route of MSC infusions.

 Additionally, MSC-derived exosomes show promise as an alternative treatment strategy. The authors call for further research, including multicenter, large-scale, long-term RCTs, to address these questions and improve the therapeutic outcomes for LC patients.

Source: Zhao, Y., Liu, Y., Zhang, W., Li, H., & Wang, L. “Efficacy and safety of mesenchymal stem cells in the treatment of liver cirrhosis: A systematic review and meta-analysis.” Stem Cell Research & Therapy, 2023. https://stemcellres.biomedcentral.com/articles/10.1186/s13287-023-03518-x.