Mesenchymal stem cell and exosome therapies for liver cirrhosis

Background: Cirrhosis is a disease in which the ability to improve fibrosis and hepatocytes regeneration gradually declines as the disease progresses. However, basic studies have revealed a mechanism of fibrosis improvement centered on macrophages. This article introduces the basic clinical studies we have conducted to improve fibrosis in cirrhosis.
Basic study: We found that mesenchymal stem cells (MSCs) migrate to the lungs and act as conducting cells. MSCs induce macrophages that act as working cells in the liver into anti-inflammatory and tissue-repairing macrophages to produce tissue repair in liver cirrhosis. We also observed that exosomes of MSCs play an important role in this process. In particular, We found that exosomes produced a high therapeutic effect similar to that of MSCs after the latter's stimulation with Interferon-gamma.
Clinical and translational study: We are currently proceeding a Phase II trial of adipose tissue-derived allogeneic MSCs for hepatitis C virus (HCV) and Non-Alcoholic SteatoHepatitis (NASH)-related decompensated cirrhosis (Phase II), and HCV, hepatitis B virus, NASH- and Alcohol-related compensated cirrhosis (Phase II). We are now accumulating results in cell therapy. For exosome therapy, we are observing exosomes' in-vivo dynamics, developing mass culture and mass collection methods, and developing mass protein concentration techniques in exosomes for clinical development.
Conclusions: Based on our understanding of the mechanisms of cirrhosis amelioration, we are developing next-generation therapies for cirrhosis.