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Int J Clin Exp Pathol 2011;4(7):692-707

Original Article
Modulation of AP-endonuclease1 levels associated with hepatic cirrhosis in rat model
treated with human umbilical cord blood mononuclear stem cells

Ahmad R Bassiouny, Amira Z Zaky, Shaymaa A Abdulmalek, Kamal M Kandeel, Alaa Ismail, Marie Moftah

Department of Biochemistry, 3Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Surgery Department, Faculty of
Medicine, Ain Shams University, Cairo, Egypt.

Received September 6, 2011; accepted October 15, 2011; Epub October 16, 2011; Published October 31, 2011

Abstract: Oxidative stress in liver cells may contribute to the etiology of hepatic diseases, as in liver cirrhosis. AP-Endonuclease1 (APE1/Ref-1)
is essential for cell protection toward oxidative stress by acting as a transcriptional regulator of pro-survival genes and as a redox sensitive
protein. The aim of this study was to critically analyze the various parameters governing the success of human umbilical cord blood
mononuclear stem cell-based (MNCs) therapy without the use of an immunosuppressant and to investigate for the first time the expression of
APE1 during thioacetamide (TAA)-induced cirrhosis and MNCs therapy in a rat model. Umbilical cord blood samples from full-term deliveries
were collected. Lethal fulminant hepatic cirrhosis in rats was induced by intraperitoneal injection of thioacetamide. MNCs were then
intrahepatically transplanted. We measured APE1 expression at mRNA and protein levels, mRNA expression of TGF-β, α-SMA, STAP, CTGF,
MMP-9 and TIMP-1 in a follow up study. Histopathological and immunohistochemical analyses were performed 10 weeks after intrahepatic
injection of the cells. Transdifferentiated cells could be efficiently stained with antihuman hepatocytes. Interestingly, human hepatocyte-specific
markers, human albumin, cytokeratin-18 and cytokeratin-19 mRNAs were detected in rat liver after 10 days of MNCs infusion. MNC
transplanted by intrahepatic route, could engraft recipient liver, differentiated into functional hepatocytes, and rescued liver failure. Moreover up
regulation of APE1 expression confirmed by marked immunohistochemical staining may be involved in MNCs-induced hepatocytes
regeneration suggesting that maintaining high level of APE1 has protective effect as pro-survival signal.

Keywords: AP-Endonuclease1, human umbilical cord blood mononuclear stem cell, liver cirrhosis, human albumin

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Address all correspondence to:
Dr. Ahmad Bassiouny
Biochemistry Department, Faculty of Science
Alexandria University, Moharam Bake
Alexandria, Egypt.
Tel: +2012742-6041, Fax: +203391-1794
E-mail: arbassiouny@yahoo.com