Human amniotic epithelial stem cells as a new therapeutic option for portal hypertension and cirrhosis

Introduction: Portal hypertension (PH) is the most common and dreadful complication of cirrhosis. Lack of treatments promoting regression of liver cirrhosis opens the possibility of hepatic regenerative therapy through stem... [ view full abstract ]

Introduction: Portal hypertension (PH) is the most common and dreadful complication of cirrhosis. Lack of treatments promoting regression of liver cirrhosis opens the possibility of hepatic regenerative therapy through stem cells transplantation. We herein aimed at characterizing the effects of human-placenta derived stem cells in pre-clinical model of cirrhosis.

Material & Methods: Cirrhotic rats (chronic CCl₄) received 4x10⁶ viable human amniotic epithelial stem cells (hAECs; i.p.), or the corresponding vehicle (n=9 per group). After 2-week, mean arterial pressure (MAP), portal pressure (PP), portal blood flow (PBF) and hepatic vascular resistance (HVR) were measured. Liver microcirculatory function was assessed as response to incremental doses of acetylcholine. Hepatocyte and hepatic stellate cell (HSC) phenotype was characterized.

Results: hAECs-treated rats had lower PP than vehicle (12.3±1.0 vs 15.4±0.7mmHg;-20%; p=0.01), without changes in PBF, indicating decreased HVR (0.9±0.1 vs 1.4±0.2 mmHg·min·ml^-1; -36%; p=0.03). No systemic effects were observed. In addition, a markedly ameliorated liver microcirculatory function was observed in hAECs-treated rats.

Improvement in hepatic hemodynamics was associated with a significant amelioration in rat hepatocytes phenotype, evidenced by an enhanced expression of the transcription factor HNF4α (+36%) and the transporters Abcc3 (-46%) and Slc22a (+95%), and by significant improvement in biochemical parameters (serum albumin +14%, bilirubin -69%). In addition, the HSC activation marker αSMA was dramatically reduced (-70%) without changes in collagen deposition (Sirius red).

Conclusions: hAECs transplantation ameliorates the phenotype of hepatic cells in cirrhosis, leading to an improvement in portal hypertension, and therefore representing a novel therapeutic strategy for chronic liver disease.