Improvement of portal venous pressure in cirrhotic rat livers by systemic treatment with adipose tissue-derived mesenchymal stromal cells

Background aims. Portal hypertension is the main cause of complications in cirrhosis caused primarily by extensive fibrosis. Both anti-fibrotic and pro-fibrotic properties of mesenchymal stromal cells (MSCs) have been described in various animal models of liver fibrosis. Therefore, the impact of MSCs on portal hypertension and fibrosis should be investigated in an animal model of liver cirrhosis. Methods. The effect of systemic treatment with adipose tissue-derived MSCs, pre-differentiated into hepatocytic cells, was investigated in a rat model of liver cirrhosis induced by chronic inhalation of carbon tetrachloride. Results. Chronic intoxication with carbon tetrachloride increased the portal venous pressure, which was significantly attenuated by the treatment with MSCs. Consistent with the increase in portal and sinusoidal resistance in the cirrhotic liver, the splenic weight increased, which was again attenuated by the MSCs. The cells had no impact on the spontaneous improvement of liver dysfunction after cessation of treatment with carbon tetrachloride. However, fibrosis was significantly improved as assessed by image quantification of collagen stained with Sirius red. However, hydroxyproline was unchanged indicating that fibrillary collagen content was not affected. That was in line with the finding that the activation of hepatic stellate cells, mainly contributing to excess collagen production in liver cirrhosis, was not affected by the MSCs. The expression of metalloproteinases and their inhibitors did also not change. Discussion. It is suggested that hepatocytic differentiated MSCs improved portal blood flow in the cirrhotic liver rather by the physical reestablishment of liver architecture than by biochemical repair.