Deleterious Effect of Human Umbilical Cord Blood Mononuclear Cell Transplantation on Thioacetamide-Induced Chronic Liver Damage in Rats

Abstract

Our research group investigates whether human mononuclear cells isolated from umbilical cord blood (HUCBM cells) might be valuable in hepatic regenerative medicine. We recently demonstrated that HUCBM cell transplantation improves histological alterations and function of the liver in rats with acute liver damage induced by D-galactosamine. In the present study, HUCBM cells were transplanted into rats with thioacetamide (TAA)-induced liver cirrhosis, an experimental model that generates an intense fibrosis and mimics the histological and biochemical alterations found in the human disease. HUCBM transplantation had no effect on hepatic histology of cirrhotic animals. In contrast, analysis of plasma albumin and total bilirubin, liver damage markers, revealed a harmful effect of HUCBM cell transplantation in our experimental model of liver cirrhosis. Significantly higher plasma urea concentrations, marker of renal function, were observed in the cirrhotic and control rats intraportally injected with HUCBM cells than in those not receiving this therapy. Histological study revealed tubular and glomerular lesions in kidneys of cirrhotic animals transplanted with HUCBM cells. The glomeruli appeared ischemic, and the tubules showed a severe involvement that included peripheral asymmetric vacuolization and disappearance of the tubular lumen. Taken together, the histological and biochemical data suggest that the cirrhotic rats subjected to HUCBM cell therapy developed a hepatorenal syndrome.Key words: Cell transplantation; Fibrosis; Human mononuclear cells; Liver cirrhosis; Thioacetamide; Umbilical cord blood INTRODUCTIONcurrently being investigated in regenerative medicine of the liver, and numerous groups have studied the transplantation of hepatocytes in experimental models of Liver diseases affect approximately 17% of the world population and entail high social costs (11). Whole liver liver disease (8,14). Similar experiments have been performed in humans in various countries, with encouragtransplantation, the current therapy for end-stage hepatic disease, is limited by the shortage of organ donors (20).ing results (3,5,19). Hematopoietic stem cells from bone marrow (BMSC) Furthermore, there is no specific treatment for the liver fibrosis that develops in chronic hepatic diseases, reor umbilical cord blood (UCBSC) are also being tested for this purpose. BMSC gave rise to functional hepatogardless of their etiology (22). Accordingly, novel therapies are required to alleviate the suffering of many pacytes in the liver of mice with tyrosinemia (9), and UCBSC produced similar results in mice with liver damage due tients.Cell transplantation represents one new therapeutic to overexpression of Fas ligand (13 (17,18), and were found to improve human liver funcwhereas the control group (n = 46) received water for the same time period (4,16). tion in noncontrolled and nonrandomized phase I clinical trials (6,21).Transplantation Experiments Our research group investigates whether human mononuclear cells isolated from umbilical c...

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