MSCs augment liver regeneration after paracetamol-induced acute liver injury by their anti-apoptotic and pro-proliferative mode of action

Paracetamol (acetaminophen) intoxication is the most common cause of acute liver failure, consequently liver transplantation is acquired.Because there is a deficit of donor organs, new feasible therapeutic approaches are necessary.Thus, the aim of the study was to establish a rat model of acetaminophen intoxication and to proof the potential of mesenchymal stem cells (MSCs) to promote liver regeneration after this toxic challenge.In 7 weeks old F344 (DPPIV-/-) Fischer rats acute liver failure was induced by 3 oral doses of 4g/kg bw acetaminophen. 6h after the final dose MSCs were administered systemically by tail vein injection. To verify the hepatic damage, activity of serum transaminases (ASAT/ALAT) was determined and histological stainings (HE, AIF, GS, TUNEL) were performed.6 hours after the third acetaminophen administration an acute liver intoxication was manifest. ASAT and ALAT activities were elevated significantly. Furthermore necrotic areas were visible in HE stains of liver sections. Apoptotic hepatocytes stained with AIF (Apoptosis-inducing factor) were visible in the perivenous regions of the liver lobule, which was evidenced by staining of glutamine synthetase (GS). 12 hours after application of MSC the apoptotic, TUNEL positive cells were significantly decreased as compared with animals receiving PBS instead of MSCs. Hence, MSCs supported regeneration of the damaged liver by reducing hepatocyte apoptosis.Systemically administered MSC homed to the liver. They contributed to liver regeneration after acetaminophen-induced acute injury by the attenuation of drug-induced apoptosis. Thus, stem cell therapy in cases of acute liver diseases might be a feasible novel therapeutic option.

MSCs - anti-apoptotic - paracetamol