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Transplantation of endothelial progenitor cells ameliorates vascular dysfunction and portal hypertension in carbon tetrachloride‐induced rat liver cirrhotic model
Author(s) -
Sakamoto Masaharu,
Nakamura Toru,
Torimura Takuji,
Iwamoto Hideki,
Masuda Hiroshi,
Koga Hironori,
Abe Mitsuhiko,
Hashimoto Osamu,
Ueno Takato,
Sata Michio
Publication year - 2013
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2012.07238.x
Subject(s) - medicine , portal hypertension , enos , portal venous pressure , cirrhosis , progenitor cell , transplantation , liver transplantation , endocrinology , endothelial progenitor cell , pathology , endothelial nos , nitric oxide synthase , stem cell , nitric oxide , biology , genetics
Background and Aim In cirrhosis, sinusoidal endothelial cell injury results in increased endothelin‐1 ( ET ‐1) and decreased nitric oxide synthase ( NOS ) activity, leading to portal hypertension. However, the effects of transplanted endothelial progenitor cells ( EPCs ) on the cirrhotic liver have not yet been clarified. We investigated whether EPC transplantation reduces portal hypertension. Methods Cirrhotic rats were created by the administration of carbon tetrachloride ( CCl 4 ) twice weekly for 10 weeks. From week 7, rat bone marrow‐derived EPCs were injected via the tail vein in this model once a week for 4 weeks. Endothelial NOS ( eNOS ), vascular endothelial growth factor ( VEGF ) and caveolin expressions were examined by W estern blots. Hepatic tissue ET ‐1 was measured by a radioimmunoassay ( RIA ). Portal venous pressure, mean aortic pressure, and hepatic blood flow were measured. Results Endothelial progenitor cell transplantation reduced liver fibrosis, α‐smooth muscle actin‐positive cells, caveolin expression, ET ‐1 concentration and portal venous pressure. EPC transplantation increased hepatic blood flow, protein levels of eNOS and VEGF . Immunohistochemical analyses of eNOS and isolectin B 4 demonstrated that the livers of EPC ‐transplanted animals had markedly increased vascular density, suggesting reconstitution of sinusoidal blood vessels with endothelium. Conclusions Transplantation of EPCs ameliorates vascular dysfunction and portal hypertension, suggesting this treatment may provide a new approach in the therapy of portal hypertension with liver cirrhosis.