In vivo study of the role of mesenchymal stem cells on liver fibrogenesis

Atoosa Gitiara,1,* Sogol mazhari,2 Kaveh baghaei,3 Behzad hatami,4 Ali asadi rad,5 Afshin moradi,6

1. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
6. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

Introduction

Liver fibrosis has been affected by excessive accumulation of extracellular matrix (ecm) proteins such as α-sma, collagen i and iii result in liver failure. besides viral infections and alcohol consumption as the common causes of liver fibrosis, non-alcoholic steatohepatitis (nash) is one of the main cause which can present as pre-stage of cirrhosis and hepatocellular carcinoma (hcc). the process of liver fibrosis has been leading up to the secretion of many pro-inflammatory factors. mesenchymal stem cells (mscs) represent a population of adult stem cells, which have a fibroblast-like shape. mscs are capable of secretion immunomodulatory cytokines causing anti-inflammatory effects liver fibrosis. in current study we aim to study the role of these cells on liver fibrosis by using induced fibrosis animal model.

Methods

5 male sprague dawley rats, approximately 8-10 weeks old weighing 200±50g prepared and were utilized to induce liver fibrosis by twelve intraperitoneal injection of ccl4 for six weeks. 24 hours after the last dose of ccl4, rats were treated by the single-injected form of mesenchymal stem cells in tail vein. at the end of the 6-week treatment period, all the rats were sacrificed. the blood was collected for measuring the serum markers. specimens were cut out from the liver for evaluation of histopathological observation and molecular marker tests.

Results

Determination of alanine aminotransferase (alt), aspartate aminotransferase (ast), and alkaline phosphatase (alp) as hepatic enzymes is a solution to diagnose liver health. the mscs treated rats, confront to the reduction amount of alt, ast and alp in comparison with ccl4 treated group. furthermore, the amount of fibrosis-related genes such as procollagen i and iii, laminin and α-sma, decreased in mscs treated group in real-time pcr analysis. pathological observations by h&e staining showed less pseudolobule forms and less collagen fibers due to the decrease of liver fibrosis by mscs

Conclusion

The result of serology test, real-time pcr and histopathology analysis demonstrated that fibrotic factors were reduced effectively in mscs treatment in comparison with ccl4 group. according to the broad activities of mscs, the administration of mscs can salvage patients with fibrotic liver by improving hepatocytes function.

Keywords

Liver fibrosis, ccl4, mesenchymal stem cells, histopathology analysis, real-time pcr, serum markers.