Transplantation of human CD34+ stem cells from umbilical cord blood to rats with thioacetamide-induced liver cirrhosis.
BACKGROUND
Liver fibrosis results from accumulation of extracellular matrix components and is associated with many chronic hepatic diseases. There is to date no specific therapy for this disease, and patients receive treatment for its associated complications. Specific progenitor cells, known as oval cells, are present in the liver. As oval cells express markers such as CD34, they are thought to arise from a hematopoietic precursor. The aim of this work was to investigate whether transplantation of hematopoietic CD34(+) stem cells could improve hepatic fibrosis by their differentiation into hepatocytes.


METHODS
CD34(+) stem cells from human umbilical cord blood were purified, transduced with a lentiviral vector containing the green fluorescent protein (GFP) gene and injected via portal vein into rats with liver cirrhosis induced by the 4-month administration of thioacetamide. Rats were killed 15 and 60 days post-transplantation.


RESULTS
Up to 37% and 22% fluorescent cells were observed in the blood of control and cirrhotic rats, respectively, at 15 days post-transplantation. At 60 days post-transplantation, however, fluorescent cells were completely absent from the blood. Fluorescence was not detected in liver sections at either 15 or 60 days post-transplantation. Polymerase chain-reaction study to detect the GFP gene ruled out silencing of the transgene.


CONCLUSIONS
These results suggest that the transplanted cells did not engraft in the liver and were eliminated from the rats.
Sáez-Lara
María José
MJ
Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Granada, Granada, Spain.
Frecha
Cecilia
C
Martín
Francisco
F
Abadía
Francisco
F
Toscano
Miguel
M
Gil
Angel
A
Fontana
Luis
L
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology*; D002460:Cell Line; D002469:Cell Separation; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000276:immunology* / Q000601:surgery*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D013853:Thioacetamide / Q000494:pharmacology*; D014183:Transplantation, Heterologous / Q000276:immunology
D018952:Antigens, CD34; D013853:Thioacetamide