5 Under all conditions and with all the types of stem/progenitors identified, the edges of the colonies contained cells that were larger and more differentiated than those in the colony interiors mimicking the formation of liver tissue from ductal plates4 and that of islets from

the edges of pancreatic ducts during organogenesis.11 Biliary tree stem/progenitors are logical precursors for mature cells of liver, bile duct, and pancreas given known events in organogenesis and in studies on pathologies of these tissues.6 They overcome many, if not all, of the ongoing controversies Antiinfection Compound Library purchase about whether or not there are stem cells in adult tissues for pancreas.11 The inability to identify true stem cells in adult pancreas10, 11, 23, 24 has fueled attempts to lineage restrict ES cells, induced pluripotent stem (iPS) cells, amniotic fluid-derived stem cells (AFSCs), or mesenchymal stem cells (MSCs), often with genetic manipulation to direct these cells to an endodermal fate; to find ways to reprogram adult pancreatic acinar cells; or to elicit proliferation of existing pancreatic islet beta cells.11, 25, 26 The process of driving Sunitinib mw these various stem cell populations to a

mature endodermal tissue fate is inefficient, requiring up to 4-6 weeks in culture, and yielding adult cells with muted functions or with overexpression of or absence of expression of some genes. In the cases of the MSCs, the resulting adult cells are phenotypic hybrids of mesenchymal cells and the desired adult cell type.27 Moreover, for reasons unknown, the phenotype of the adult cells generated is distinct with every preparation and source. Fully mature hepatocytes or glucose-regulated MCE公司 β-cells from these precursors occur only with in vivo maturation of transplanted cells after several months. Moreover, any therapy based on ES or iPS cells may be limited by the potential of teratoma formation, usually ascribed to residual

undifferentiated stem cells.28, 29 Our findings that there are endodermal stem/progenitors in the biliary trees of all donor ages; that they clonogenically expand in vitro under wholly defined conditions; and that they readily and efficiently lineage restrict to liver, biliary tree, or pancreatic adult fates in culture with sets of wholly definable microenvironmental cues or in vivo suggest that they will become preferred choices for clinical programs and most experimental studies. The speed at which the differentiation occurs, even in culture, is an indication that these biliary tree stem/progenitors have progressed through most of the developmental stages for a liver or pancreatic fate. Indeed, their phenotypic characteristics in situ and in vitro indicate that they are mostly at stage 4 of the 5 stages during the progress of human ES cell stepwise-differentiation toward an islet fate.