Stem Cell Transplant for Advanced Stage Liver Disorders: Current Scenario and Future Prospects

Chronic Liver Disorders (CLD), caused by the lifestyle patterns like alcoholism or by non-alcoholic fatty liver disease or because of virus-mediated hepatitis, affect a large population fraction across the world. CLD progresses into end-stage diseases with a high mortality rate. Liver transplant is the only approved treatment available for such end-stage disease patients. However, the number of liver transplants is limited due to the limited availability of suitable donors and the extremely high cost of performing the procedure. Under such circumstances, Stem Cell (SC) mediated liver regeneration has emerged as a potential therapeutic alternative approach.

This review aims to critically analyze the current status and future prospects of stem cellbased interventions for end-stage liver diseases. The clinical studies undertaken, the mechanism underlying therapeutic effects and future directions have been examined.

The clinical trial databases were searched at https://clinicaltrials.gov.in and http://www.isrctn.com to identify randomized, non-randomized and controlled studies undertaken with keywords such as "liver disorder and Mesenchymal Stem Cells (MSCs)", "liver cirrhosis and MSCs" and "liver disorder and SCs". Furthermore, https://www.ncbi.nlm.nih.gov/pubmed/ database was also explored with similar keywords for finding the available reports and their critical analyses.

The search results yielded a significant number of studies that used bone marrow-derived stem cells, MSCs and hepatocytes. The studies clearly indicated that SCs play a key role in the hepatoprotection process by some mechanisms involving anti-inflammation, auto-immune-suppression, angiogenesis and anti-apoptosis. Further, studies indicated that SCs derived paracrine factors promote angiogenesis, reduce inflammation and inhibit hepatocyte apoptosis.

The SC-based interventions provide a significant improvement in patients with CLD; however, there is a need for randomized, controlled studies with the analysis of a long-term follow-up.