Deleterious effect of human umbilical cord blood mononuclear cell transplantation on thioacetamide-induced chronic liver damage in rats.
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.
Alvarez-Mercado
Ana I
AI
Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja, 18071 Granada, Spain.
García-Mediavilla
María V
MV
Sánchez-Campos
Sonia
S
Abadía
Francisco
F
Sáez-Lara
María J
MJ
Cabello-Donayre
María
M
Gil
Angel
A
González-Gallego
Javier
J
Fontana
Luis
L
D000410:Alanine Transaminase / Q000097:blood; D000418:Albumins / Q000032:analysis; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects*; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology*; D006530:Hepatorenal Syndrome / Q000209:etiology / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide; D014508:Urea / Q000097:blood
D000418:Albumins; D015415:Biomarkers; D013853:Thioacetamide; D014508:Urea; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D017493:Leukocyte Common Antigens; D001663:Bilirubin