Early Transplantation of Human Umbalical Cord Blood Stem Cell Can Improve Engrafment and Liver Response to Carbon Tetra Chloride induced Cirrhosis in Mice

Document Type : Original Article

Authors

1 Department of Physiology, Suez Canal University

2 Department of Pathology, Suez Canal University

3 Department of Internal Medicine, Suez Canal University

Abstract

Background: The potential use of UCB in the treatment of hepatic failure (a major
problem worldwide) has been a research focus for several years now. Recent studies
have identified UCB as a possible source of hepatic progenitor cells that can be
differentiated into hepatocyte in vitro and in vivo and can ameliorate fibrosis.
Objectives: the aim of this study was to investigate the hepatic response to
transplantation of HUCB stem cells in CCl4 injured liver in mice, as regard liver
function, histopathology and immunohistochemistry. Design: Experimental study.
Setting: The stem cell unit in the Physiology Department and the animal house after
cord blood collection in the Gynecology and Obstetric department, Faculty of
Medicine, Suez Canal University. Materials and Methods: Hepatic fibrosis was
induced by CCl4. HUCB stem cells were infused systemically through the tail vein
immediately (group 1), and after one week of receiving CCl4 (group 2), Group 3
received only CCl4 (as a control group). Administration of CCl4 was continued for 10
weeks in G1, G2 and G3, while group 4 (as another control group) received only the
solvent of CCl4 for 10 weeks. After that, blood from all groups was collected for
assessment of liver function, then all mice were sacrified under general anesthesia
and the liver was fixed and prepared for histopathological and immumohistochemical
examination. Results: It was found that the level of alanine aminotransferase (ALT) in
mice treated with stem cells after CCl4 administration was significantly lower while
serum albumin was significantly higher compared to group 3 animals who received
CCl4 without stem cells treatment (P= 0.001). Whereas serum total and direct
bilirubin levels were similar among all groups. histopathological examination
revealed that hepatic damage was less in the stem cells treated mice (G1 and G2) than
in non treated group (as regards liver cell changes, portal tract inflammation,
piecemeal necrosis, portal tract fibrosis and bridging fibrosis). However, liver
inflammation and fibrosis were more in mice treated after one week than in
immediately treated mice. Immumohistochemical examination, more importantly, IHC
staining with monoclonal mouse anti-human hepatocyte revealed presence of human
hepatocytes in injured mice liver which proved that the transplanted stem cells were
transdifferentiated into hepatocyte. Conclusion: HUCB stem cells were
transdifferentiated into hepatocyte when infused in mice injured liver and cause
improvement in liver function test and liver histology.

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