Adipose-derived mesenchymal stem cells slow disease progression of acute-on-chronic liver failure

• DOI: 10.1016/j.biopha.2017.04.117
• Publication Date: 2017-05-11T13:07:17Z
• Authors: Carlos Gilsanz; Maria-Angeles Aller; Sherezade Fuentes...; Isabel Prieto; Alejandro Blázque...; Salvador Argudo; Jorge Fernández-D...; Jose Beleña; Jaime Arias; María P. De Miguel
• Keywords: Male; 0303 health sciences; Body Weight; Acute-On-Chronic Liver Failure; Cell Differentiation; Mesenchymal Stem Cells; Kaplan-Meier Estimate; Organ Size; Mesenchymal Stem Cell Transplantation; Survival Analysis; 3. Good health; 03 medical and health sciences; Liver; Disease Progression; Animals; Humans; Rats, Wistar

A serious complication of chronic hepatic insufficiency is acute-on-chronic liver failure, a recognized syndrome characterized by acute decompensation of cirrhosis and organ/system failure. We investigated the use of adipose-derived mesenchymal stem cells (AD-MSCs) in an experimental model of acute-on-chronic liver failure, developed by microsurgical extrahepatic cholestasis in rats. Rats undergoing microsurgical extrahepatic cholestasis were treated by intraparenchymal liver injection of human or rat AD-MSCs, undifferentiated or previously differentiated in vitro toward the hepatocyte lineage. The groups treated with rat AD-MSCs showed less ascites, lower hepato- and splenomegaly, less testicular atrophy, and an improvement in serum biochemical hepatic parameters. There was also an improvement in histological liver changes, in which the area of fibrosis and bile duct proliferation were significantly decreased in the group treated with predifferentiated rat AD-MSCs. In conclusion, an isograft of hepatocyte-predifferentiated AD-MSCs injected intraparenchymally 2 weeks after microsurgery in extrahepatic cholestatic rats prevents secondary complications of acute-on-chronic hepatic failure. These data support the potential use of autologous AD-MSCs in the treatment of human cholestasis, and specifically of newborn biliary atresia, which could be beneficial for patients awaiting transplant.