Effect of Human Umbilical Cord Blood Stem Cells on Hepatic Regeneration and Immune Response in Liver Fibrosis in Rats

Abstract

To study the effect CD34+, CD34- and mononuclear cells in a rat model of liver fibrosis, 65 adult female albino rats were divided into 5 equal groups. Group I served as control, while hepatic fibrosis was induced in the other 4 groups by subcutaneous injection of CCl4 for 8 weeks. Group II did not receive any treatment while groups III, IV and V were treated by CD34+ stem cells, CD34- fraction, or mononuclear cells, respectively, as a single IV injection. Liver function and fibrosis were assessed by serum levels of AST, ALT, GGT, albumin and procollagen III. At the end of the experiments the liver was extracted for immunohistochemical (IHC) detection of homing and immune-response markers, as well as for histopathological study. There was a significant improvement of serum levels of AST, ALT and GGT in the 3 treated groups, whereas serum albumin and procollagen III did not show significant change. Histopathology showed improvement in hepatic damage in the stem cell treated rats. IHC staining showed positive staining for cytokeratin 19, human CD34 and human albumin. IHC staining with monoclonal mouse anti-rat CD68, CD8 and CD4 showed no differences among the 3 groups treated with stem cells. We conclude that HUCB stem cells were transdifferentiated into hepatocytes when transplanted in rats with an injured liver and improved liver functional and structural alterations without stimulating a significant immune response.