OBJECTIVESTo study the effects of rat endothelial progenitor cell (EPC) transplantation on hepatic fibrosis in carbon tetrachloride (CCl4) induced hepatic fibrosis rats.

METHODSHepatic fibrosis was developed in 24 healthy female SD rats by feeding them 25% CCl4/olive oil for 8 weeks. Eight of them were sacrificed at the end of the 8 weeks. The rats were subdivided into a EPCs transplanting group (n=8) and a saline control group (n=8). After the EPCs were isolated and cultured for 9 days, the cells were injected into the portal veins of the rats in the EPCs transplanting group. Four weeks later all of the rats were sacrificed. The blood biochemical parameters from the serum were examined. The degree of liver fibrosis was evaluated by reading Masson staining liver slides and by detecting the expression of a-SMA and collagen III.

RESULTSCompared with the saline control group, hepatic activity index (HAI), levels of ALT, AST and TBil in the serum were all lower in the EPCs transplanting group, but the level of Alb was higher and the expression of a-SMA and collagen III were lower. Compared with the 8 week hepatic fibrosis group, the levels of ALT, AST and TBil in the serum of the EPCs transplanting group were all lower. In the saline control group, the serum levels of ALT, AST and TBil were higher, the level of Alb was lower, and the expressions of a-SMA and Collagen III were higher.

CONCLUSIONIn hepatic fibrosis rats, transplantation of rat EPCs could minimize the hepatic fibrosis process and the injuries.

Animals ; Carbon Tetrachloride ; Endothelial Cells ; cytology ; Female ; Liver Cirrhosis, Experimental ; chemically induced ; pathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Stem Cell Transplantation

Loss of transforming growth factor (TGF)-beta signaling has been implicated in malignant transformation of various tissues. Smad4 plays a central role in the signal transduction of TGF-beta. Deletion or mutation of Smad4 has been described in a number of cancers. This study was aimed to investigate a potential role of Smad4 in leukemia including its expression and location in blast cells. The mononuclear cells were separated from bone marrow of leukemia patients. The samples, blast cells of which were more than 90% in mononuclear cells, were selected. The expression and location of Smad4 protein were analyzed by immunohistochemistry methods. The results showed that the Smad4 protein located mainly in nucleus, part of this protein located in cytoplasma, the expressions of Smad4 were not detected in 6 out of 9 ALL patients, in 7 out of 24 AML patients and in 1 out of 2 CML patients; these leukemia patients, in whose cells the expression of Smad4 was not detected, included one L1 and one L3, four L2, one M0, one M1, two M2a, one M3a, one M4b, one M6 and one CML. In conclusion, the Smad4 protein was mainly in nucleus, the deletion or functional change of Smad4 may related with the pathogenesis of human AML.
Humans ; Leukemia, Myeloid, Acute ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Signal Transduction ; Smad4 Protein ; biosynthesis ; genetics ; Transforming Growth Factor beta ; biosynthesis ; genetics