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This journal is published by the University Library System of the University of Pittsburgh as part  

of its D-Scribe Digital Publishing Program and is cosponsored by the University of Pittsburgh Press. 

 

 

 

 

 

 

 
 

 

 

 

Ectopic Liver Tissue Formation in 

Rats with Induced Liver Fibrosis 

 

Bauyrzhan Umbayev1, Andrey 

Tsoy1, Tamara Shalakhmetova2, 

Sholpan Askarova1 

 
1Center for Life Sciences, Nazarbayev 
University, Astana, Kazakhstan; 
2Department of Biology and 
Biotechnology, Al-Farabi Kazakh National 
University, Almaty, Kazakhstan 

 

 

 

 

 

 

 

 

 

 

 

 

Vol. 3, Suppl. (2014)   |   ISSN 2166-7403 (online)    

DOI 10.5195/cajgh.2014.180   |   http://cajgh.pitt.edu 

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UMBAYEV 

 

 

This work is licensed under a Creative Commons Attribution 4.0 United States License. 

 

This journal is published by the University Library System of the University of Pittsburgh as part  

of its D-Scribe Digital Publishing Program and is cosponsored by the University of Pittsburgh Press. 

 

Central Asian Journal of Global Health 

Volume 3, Suppl. (2014)  |  ISSN 2166-7403 (online)  |  DOI 10.5195/cajgh.2014.180  |  http://cajgh.pitt.edu 

  

 

Abstract 

Introduction: The possible alternative approach to whole-organ transplantation is a cell-based therapy, which can also be used as 

a "bridge" to liver transplantation.  However, morphological and functional changes in the liver of patients suffering from chronic 

liver fibrosis and cirrhosis restrict the effectiveness of direct cell transplantation. Therefore, extra hepatic sites for cell 

transplantation, including the spleen, pancreas, peritoneal cavity, and subrenal capsule, could be a useful therapeutic approach for 

compensation of liver functions. However, a method of transplantation of hepatocytes into ectopic sites is needed to improve 

hepatocyte engraftment. Previously published data has demonstrated that mouse lymph nodes can support the engraftment and 

proliferation of hepatocytes as ES and rescue Fah mice from lethal liver failure. Thus, the aim of the study was to evaluate the 

engraftment of i.p. injected allogeneic hepatocytes into extra hepatic sites in albino rats with chemically induced liver fibrosis (LF).  

Materials and methods: Albino rats were randomly divided into 4 groups: (1) intact group (n = 18); (2) rats with induced LF (n 

= 18); (3) rats with induced LF and transplanted with hepatocytes (n = 18); (4) as a control, rats were treated with cyclosporine A 

only (n = 18). In order to prevent an immune response, groups 2 and 3 were subjected to immunosuppression by cyclosporine A 

(25 mg/kg per day). LF was induced using N-nitrosodimethylamine (NDMA), i.p., 10 mg/kg, three times a week for 4 weeks and 

confirmed by histological analysis of the liver samples. Hepatocytes transplantation (HT) was performed two days after NDMA 

exposure cessation by i.p. injection of 5×106 freshly isolated allogeneic hepatocytes. Liver function was assessed by quantifying 

blood biochemical parameters (ALT, AST, GGT, total protein, bilirubin, and albumin) at 1 week, 1 month, and 2 months after 

hepatocytes transplantation (HT). To confirm a hepatocytes’ engraftment, we conducted immunohistochemical staining against 

HepPar1.  

Results: We observed a 30% mortality rate among rats with LF within 1 week after NDMA exposure cessation, while 100% of 

animals with HT survived. ALT, AST, and GGT activities and bilirubin levels were markedly elevated in blood samples of LF rats 

compared to the control animals. However, HT significantly improved ALT, AST, and GGT activity as well as bilirubin levels. 

We also observed decreased levels of total protein and albumin in the blood serum of rats with LF, while HT normalized these 

parameters. At the same time, we have not detected any statistical differences of the studied parameters in the group 4, which was 

treated with Cyclosporine A only, compared with the intact animals. HepPar1 immunohistochemical staining of the different tissue 

sections demonstrated the presence of engrafted hepatocytes, mainly within enlarged Peyer's patches (aggregated lymphoid nodules 

in the lowest portion of the small intestine).  

Conclusion: The results of our study provide evidence that HT improves animal survival and liver functions. One potential reason 

for these results is that ectopic hepatic mass inside the Peyer's patches can rescue rats from liver failure. 

Keywords: ectopic liver tissue, chronic liver fibrosis, transplantation  

 

 

 

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