The stem cells in chronic experimental liver diseases

Abstract

Introduction: Chronic liver diseases (CLD) are increasing worldwide affecting almost 17% of general population."In the Republic of Moldova during the last ten years the incidence and prevalence of CLD had increased continuously. The liver cirrhosis in our country is the third cause of death after cardiovascular diseases and cancer. Ihis situation is the result of a high prevalence of infectious viral hepatitis, alcohol and hepatotoxic drug abuse, and the unavailable so far of the orthotopic liver transplantation (OLT), the only curative treatment for rhe end stage liver diseases. The number of patients waiting for an OLT has increased during the last years, meanwhile the organ donation has not kept up with demand. Consequently the organ shortage is increasing the morbidity and mortality of patients on waiting list. This clearly implies the need for finding alternative solutions for the patients with end stage liver disease, and stem ceil therapy is the one that gives the most hope so far. The aim ot this study was to induce chronic experimental liver disease in rats, then transplant stem cells and further evaluate the effect on liver function. Material and methods: Chronic liver lesions were induced on white female rats of 6-8 months age, weighting 210-250 mg, by injecting CCL4 subcutaneously, dissolved in olive oil, twice a week, for 8 weeks. At the end of 6 weeks the rats were divided into 5 groups with further intrasplenic transplantation of 6xl03 allogenic stem cells (SC) performed. The animals in group 1 received blood marrow SC, the second group received umbilical cord SC, the third group received hepatic fetal SC. The fourth and fifth groups received intrasplenic saline solution only. Meanwhile we continue to inject CCL4 subcutaneously twice a week for the groups 1,2,3 to prevent endogenous liver regeneration and allow the stem cells to act. For the fourth group we continue with CCL4 and for the 5 without CCL4 to allow endogenous regeneration for another 6 weeks. The animals were sacrificed at 10, 20 and 40 days after transplantation, and there were collected 5 ml of blood and the liver specimens. Preventive results: After 6 weeks of CCL4 administration 90% of rats presented weight loss ranging between 5 to 20%, and signs of coagulopathy like periocular bleeding. The 6 rats sacrificed just before the SC transplantation proved the presence of ascites and yellow, nodular liver changes. Histological examination showed the presence of infiltration of the liver with neutrophils, regenerating nodules of hepatocytes and the deposition of connective tissue between these nodules. Conclusions: Further biochemical, histological and immunohystochemical analyses have to be done on liver specimen and collected blood to evaluate the effects of SC therapy on the end stage of the liver disease.