Introduction: Clinical intraportal hepatocytes transplantation is controversial option in the advanced chronic liver disease. Extraembryonic mesenchymal stem cells (MSC) possess multipotency and remarkable immunomodulatory features with robust and constitutive anti-inflammatory and anti-fibrotic properties, making them suitable for the treatment strategy of different acute and chronic liver disorders. The aim of this study was to evaluate the safety and the therapeutic potential of systemic intravenous placental MSCs infusion and human hepatocytes intrapotal transplantation combined with placental MSCs for the treatment of decompensated liver cirrhosis.
Method: Placental MSCs were obtained from the placenta of a healthy woman in labour who signed an informed consent and was delivered by caesarean section. The chorionic plate as a source of MSC was chosen based on the high differentiation potential and more significant hepatocyte growth factor secretion. Human hepatocytes were obtained and criopreserved from not used deceased donor livers. There are two different therapiutic  approaches: intravenous systemic placental MSCs infusion (~2mln per kg) (group 1) and local intraportal transjugular hepatocytes tansplantation (HTr) (10 mln per kg), combined with placental MSCs (2 mln per kg) for better engraftment and hepatocytes viability (group 2). In prospective study 33 patients with advanced decompensated liver cirrhosis awaiting liver transplantation were included (17 in interventional group and 16 in the control group); in 17 cell therapy patients  (age – 42 (28-67); MELD score – 28 (11-35)), 14 were in the group 1 and 3 - in the group 2.  
Results: Systemic administration of placental MSC did not cause side effects, was not associated with complications of administration or worsening of the clinical picture. Laboratory effectiveness of therapy was confirmed by a significant decrease in the level of total bilirubin by an average of 133 mmol/l from the maximum value (39%). There was an increase in total protein after therapy by 6 g/l (11%), as well as stabilization of coagulopathy (a decrease in the international normalized ratio (INR) by 0.37 (25%). In one case of HTr (with portal pressure of 32 mm Hg), the deterioration of portal hypertension (variceal bleeding and hepatic encephalopathy progression) occured; therefore, in case of high portal pressure, HTr should be combined with TIPS procedure. Totally, liver transplantation was performed in 41% (7 out of 17) interventional group patients.
Conclusion: Systemic intravenous placental mesenchymal stem cells infusion is safe and effective strategy for acute on chronic liver failure stabilization. The presence of severe portal hypertension limits the use of hepatocytes transplantation. Systemic stem cell therapy may be used as a bridge for liver transplantation in urgent patients group from thr waiting list.