Abstract
Hepatocirrhosis is one of the most severe complications of chronic hepatic disease in terms of medical intervention, and the available therapies are limited and not very successful. In this study, bone marrow-derived mesenchymal stem cells (BM-MSCs) from host rats were transduced with an adenoviral vector labelled with green fluorescent protein (EGFP) to overexpress hepatocyte growth factor (HGF). The therapeutic effect of these modified stem cells (HGF-BM-MSC group) transplanted intravenously into hepatocirrhosis model rats treated with CCl4 was evaluated using serological, biochemical and histological approaches. We compared the rats in the HGF-BM-MSC group with those in the other groups (rats treated with BM-MSCs, rats treated with HGF and untreated rats (Controls)) in detail. The localisation of EGFP-tagged BM-MSCs in the injured liver was evaluated using a microscope, and the cells co-expressed hepatocyte nuclear factor 4α, albumin and cytokeratin 18. After treatment for 4 weeks, the HGF-BM-MSC, BM-MSC and HGF groups exhibited increased protein and mRNA levels of hepatocyte nuclear factor 4α, albumin and cytokeratin 18, but decreased levels of aspartate aminotransferase, alanine aminotransferase and total bilirubin. These findings indicate that BM-MSC transplantation and HGF application have great potential for the treatment of hepatocirrhosis.
Highlights
Cirrhosis is a common hepatic disease that can be caused by chemical injury or viral infection in the liver
CCl4-induced cirrhotic pathology in rat liver We verified the establishment of the animal model of cirrhosis by observations of haematoxylin and eosin (HE)stained liver sections from rats that survived 1 week following CCl4 or saline treatments
Hydroxyproline is an amino acid that is stably deposited in the liver and is only associated with collagenous connective tissue; it is a good substitute for the quantitative determination of collagen deposition[18]
Summary
Cirrhosis is a common hepatic disease that can be caused by chemical injury or viral infection in the liver. This disease is characterised by chronic and progressive hepatocyte degeneration and excessive fibrosis, which may lead to severe clinical outcomes, such as ascites, variceal haemorrhage and encephalopathy[1,2,3]. Many studies have shown that BM-MSCs differentiate into hepatic cells in external and internal conditions[7,8], whereas other reports have demonstrated the potential therapeutic utility of BM-MSCs in the treatment of chronic liver diseases[9,10,11]
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