Comparison of the Therapeutic Effects of hUC-MSC Intravenous Delivery and Intraperitoneal Administration of MSCs Encapsulated in Alginate Capsules for the Treatment of Rat Liver Cirrhosis

Abstract

Mesenchymal stem cells are the most promising regenerative medicine tool for treating various diseases, including liver disease, although the exact mechanism of their therapeutic action remains unclear. It was found that MSCs are captured by the lungs after systemic transplantation, quickly disappear, and are not detected at the site of injury but at the same time exhibit an obvious therapeutic effect. Comparison of the MSC efficiency depending on the route of their administration may shed light on the mechanisms involved in implementing MSC therapeutic potential. In this work, we compared the therapeutic effects of human umbilical cord MSCs (hUC-MSCs) administered systemically and intraperitoneally in the form of MSCs encapsulated in alginate capsules in a CCl4-induced model of liver cirrhosis in rats. Our study showed that both treatments resulted in liver recovery. MSC transplantation by two different routes led to a decrease in collagen deposition, the disappearance of the fibrous area by the 13th week, and the normalization of the morphometric parameters of liver parenchyma cells. In addition, the expression of some genes (EGF, alpha SMA, GFAP) which is activated in liver injury, decreased to the level observed in negative control animals. However, a detailed study of liver recovery in dynamics showed that encapsulated MSCs led to faster normalization in several parameters of the liver tissue. Our results showed that human umbilical cord MSCs effectively exhibit their therapeutic properties when using both transplantation methods. However, intraperitoneal administration of encapsulated MSCs accelerated the process of liver regeneration.