Abstract
The aim of the present study was to compare the effects of bone marrow-derived mesenchymal stem cells (BMSCs) transplanted via the portal vein or tail vein on liver injury in rats with liver cirrhosis. BMSCs were isolated from rat bone marrow and labeled with green fluorescent protein (GFP). Then, the labeled BMSCs were injected into rats with liver injury via the portal vein or tail vein. Two weeks after transplantation, three rats in each group were sacrificed to test the distribution of GFP in the liver and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin. Six weeks later, the remaining rats were sacrificed, and serum ALT, AST, albumin, hyaluronic acid (HA), laminin (LN) and procollagen type III (PC-III) levels were measured. The expression of albumin in the liver was analyzed by immunohistochemistry. Two weeks after BMSC transplantation, GFP-positive cells were detected in the livers of rats with BMSCs transplanted via the portal vein and tail vein. Compared with pre-transplantation levels, the ALT levels of the groups with BMSC transplantation via the portal vein and tail vein were significantly decreased after two and six weeks of BMSC transplantation (P<0.05), whereas the AST and albumin levels were not significantly different at two weeks after BMSC transplantation in the two groups (all P>0.05). However, the AST and albumin levels were significantly reduced at six weeks after BMSC transplantation (all P<0.05). At six weeks after BMSC transplantation, the serum HA, LN and PC-III levels in rats transplanted with BMSCs via the portal vein or tail vein had decreased significantly (all P<0.05), as compared with the levels prior to BMSC transplantation. BMSCs transplanted via the portal vein and tail vein achieved similar improvements in liver function in rats with liver cirrhosis, which suggests that peripheral venous administration is a convenient and effective route for BMSC transplantation.
Highlights
Liver injury due to chemical damage or viral infection often leads to liver fibrosis and liver failure, and this may lead to an impairment of liver function
After 48 h of culture, green fluorescent protein (GFP)‐positive Bone marrow mesenchymal stem cells (BMSCs) were observed by fluorescence microscopy, confirming that the BMSCs were labeled with GFP (Fig. 2)
The mortality rate associated with this disease is extremely high and there are no effective treatment methods for liver cirrhosis, with the exception of liver transplantation, which is limited by the availability of donor livers
Summary
Liver injury due to chemical damage or viral infection often leads to liver fibrosis and liver failure, and this may lead to an impairment of liver function. BMSC transplantation has become a novel therapeutic strategy for liver injury [2,3,4]. Certain clinical studies have suggested that BMSC transplantation is an effective treatment for patients with severe liver disease [5,6,7]. Certain issues remain to be resolved in the application of BMSC transplantation in the treatment of liver cirrhosis, such as the efficiencies of various transplantation paths, the optimum cell counts of BMSC transplantation and the timing of transplantation. BSMCs are generally transplanted via the portal vein in patients with liver diseases as the first‐pass effect in the liver is much higher than that when the transplantation is via other routes [8,9,10]. BSMC transplantation via the portal vein could transiently increase venous pressure and create a venous embolism, which would aggravate liver
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