35 In summary, we have shown that mouse iPS cells can be induced to efficiently generate intact fetal livers and that hiPS cells can be induced in culture to produce highly differentiated hepatocytes. We acknowledge that compared with the LY2157299 clinical trial in vivo environment of the liver, the conditions in culture are relatively artificial, and this is likely to impact the function of iPS-derived hepatocytes

compared with the native environment. Nevertheless, the data provided above demonstrate the feasibility of generating cells with hepatic characteristics from skin cells through an iPS cell intermediate and that such cells can engraft into the mammalian liver parenchyma. Such proof-of-concept opens up the possibility of producing patient-specific hepatocytes in a relatively simple and straightforward manner with high efficiency.

We are confident that such cells could be immediately useful for the study of hepatocellular disease and basic developmental mechanisms and for drug https://www.selleckchem.com/products/emd-1214063.html screening. The authors thank Charles Myers for providing frozen liver samples. Additional Supporting Information may be found in the online version of this article. “
“Hepatocellular carcinoma (HCC) is a highly vascularized tumor with frequent intrahepatic metastasis. Active angiogenesis and metastasis are responsible for rapid recurrence and poor survival of HCC. We previously found that microRNA-29b (miR-29b) down-regulation was significantly associated with poor recurrence-free survival of HCC patients. Therefore, the role of miR-29b in tumor angiogenesis, invasion, and metastasis was further investigated in this study using in vitro Quinapyramine capillary tube formation and transwell assays, in vivo subcutaneous and orthotopic xenograft mouse models, and Matrigel plug assay, and human HCC samples. Both gain- and loss-of-function studies showed that miR-29b dramatically suppressed

the ability of HCC cells to promote capillary tube formation of endothelial cells and to invade extracellular matrix gel in vitro. Using mouse models, we revealed that tumors derived from miR-29b-expressed HCC cells displayed significant reduction in microvessel density and in intrahepatic metastatic capacity compared with those from the control group. Subsequent investigations revealed that matrix metalloproteinase-2 (MMP-2) was a direct target of miR-29b. The blocking of MMP-2 by neutralizing antibody or RNA interference phenocopied the antiangiogenesis and antiinvasion effects of miR-29b, whereas introduction of MMP-2 antagonized the function of miR-29b. We further disclosed that miR-29b exerted its antiangiogenesis function, at least partly, by suppressing MMP-2 expression in tumor cells and, in turn, impairing vascular endothelial growth factor receptor 2-signaling in endothelial cells. Consistently, in human HCC tissues and mouse xenograft tumors miR-29b level was inversely correlated with MMP-2 expression, as well as tumor angiogenesis, venous invasion, and metastasis.