Transplantation of umbilical cord blood-derived mesenchymal stem cells to treat liver cirrhosis in mice: a comparison of tail and portal vein injection

Introduction: To date, there have been many studies indicating the positive effects of stem cells on treating liver cirrhosis. In this study, we used umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) for treatment in a mouse model of liver cirrhosis. Specifically, we determined and compared the effectiveness of two methods of MSC injection (tail vein versus portal vein).

Methods: Liver cirrhosis in male Swiss mice (of age approximately 11 weeks or under) was induced by administration of carbon tetrachloride (CCl4; 1 ml/kg). One million UCB-MSCs were then transplanted into cirrhotic mice via the portal vein or tail vein. After 21 days, blood samples were collected for measurement of transaminase, bilirubin and albumin. The expression of fibrosis-associated genes, specifically procollagen – alpha 1 and integrin – beta1, were assessed using quantitative RT-PCR. The histopathology of the specimens was also evaluated using hematoxylin/eosin, Masson trichrome staining, and immunohistochemistry using collagen type 1 and alpha-SMA antibodies.

Results: After 21 days, cirrhotic mice treated with UCB-MSCs showed recovery of bilirubin index, increase of liver albumin synthesis, inhibition of fibrosis-related gene expression (e.g. procollagen – alpha 1 and integrin – beta1), and remodeling of liver histology. From comparison of the different routes of transplantation, UCB-portal route was significantly more effective than UCB-tail route at reducing aspartate transaminase (AST) activity and bilirubin index (P<0.05), and inhibiting procollagen – alpha 1 and integrin – beta1 expression (P<0.05). UCB-MSCs from both transfusion routes showed accelerated improvement of liver histopathology.

Conclusion: Therapeutic strategies using UCB-MSCs have proven to be promising for the treatment of liver cirrhosis. Injection of UCB-MSC via portal vein was more effective than tail vein for cirrhosis treatment.