Indeed, human liver inhibitor DAPT secretase cells cultured in adipogenic differentiation medium exhibited lipid-containing droplets visualized by Oil Red staining (Figure 2(e)). Cells cultured in osteogenic differentiation media developed calcium deposits Inhibitors,Modulators,Libraries visualized by Alizarin Red staining, which is characteristic of osteogenic differentiation (Figure 2(g)). These data indicate that the liver-derived cells that propagate in vitro acquire developmental plasticity, which may allow them to differentiate along alternate developmental fates in response to applied growth and differentiation conditions. The developmental plasticity these cells exhibited may provide a partial explanation of their capacity to acquire a ��-cell phenotype in response to ectopic pancreatic transcription factor expression. 3.3.

Liver-Derived Cells Cultured In Vitro Do Not Induce Tumors in Immune Inhibitors,Modulators,Libraries Deficient Mice In Vivo The epithelial-mesenchymal transition in liver Inhibitors,Modulators,Libraries has been suggested to be related to invasiveness and metastatic potential in mouse and human cancers [39, 40]. Moreover, BM-derived mesenchymal stem cells have been demonstrated to exhibit tumorigenic capacity upon in vivo implantation [41�C43]. Therefore, we analyzed whether the implantation of adult human liver-derived cells potentially generates tumors in vivo upon transplantation in immune-deficient mice. Adult human liver-derived cells at passage 4 were injected subcutaneously Inhibitors,Modulators,Libraries into both flanks of nude mice (1 �� 106 cells per injection, 5 mice per group, 2 transplantations per mouse) and tumor growth monitored weekly.

Transplantation of tumor-derived cells, such as MDA-MB 231 or Panc-1 cells, resulted in large tumor formation 3�C6 weeks after implantation [34], but none of the mice implanted with liver-derived cells developed visible tumors over 4 Inhibitors,Modulators,Libraries months. After 17 weeks, the mice were sacrificed and the area of injection examined. No traces of the cells were identified in the specimens. These data suggest that despite the cellular plasticity manifested earlier, dedifferentiated human liver cells have mesenchymal characteristics but may not carry a risk of uncontrolled cell proliferation or tumor formation. 3.4. Irreversible Tracing of Albumin Expression The adult human-derived liver cells characterized above were reported in the past to undergo cellular reprogramming and generate insulin-producing cells upon ectopic expression of the pancreatic transcription factor PDX-1 [14, 16, 17, 30].

However, because only a fraction of PDX-1 expressing cells become insulin positive [14, 16], we sought to analyze whether the insulin-producing cells are generated from cells that originally express albumin or a yet unidentified Cilengitide side population of stem-like cells that may be enriched in the hepatic-derived primary cultures. Because PDX-1 turns off the hepatic repertoire of gene expression [30], we irreversibly tagged albumin expression prior to PDX-1 treatment.