The microenvironment drives the cells rapidly to a specific adult fate that can be easily identified by morphology and functions. Further differentiation occurs with or without selective pressure in vivo. That for lineage restriction toward the intrahepatic parenchymal cell fates resulted in rapid differentiation, because the in vivo environment is toward integration of the cells within the liver plates followed by differentiation and with minimal adverse variables. Epigenetics Compound Library high throughput By contrast, that for pancreatic islets in hosts with STZ-induced diabetes involved selective pressure for differentiation in combination

with adverse effects of the toxic environment induced by hyperglycemia. Blood vessels can become narrowed or blocked by a buildup of fat and cholesterol due to abnormal glucose metabolism and poor nutrient conditions in hyperglycemic environment. Transplanted precursors for pancreatic islets selleck compound can take months to fully mature given this mix of positive and negative effects resulting from hyperglycemia, as has been shown by others.28 Thus, the speed

of differentiation achieved in vitro versus in vivo is distinct for each adult fate being generated and dependent on the balance of positive and adverse effects of the in vivo microenvironment. We interpret the survival and rescue of the transplanted mice from hyperglycemia as due to the production of human insulin. One cannot exclude the possibility that some degree of spontaneous regeneration of C59 solubility dmso the mouse pancreas might have occurred, resulting in the regeneration of endogenous islets releasing murine insulin, but even if this occurred it was insufficient to rescue the sham controls. The controls subjected to STZ maintained glucose levels above 750 mg/dL throughout the experiments, and some of them died. One cannot consider the option of formation of hybrids between host pancreatic islet cells and the biliary tree-derived islet-like clusters,

because transplantation was done into the fat pads. The strongest evidence is that the dramatic reduction in hyperglycemia in the experimental mouse correlated with increasing levels of human insulin/C-peptide in their blood, and that the levels were regulatable by glucose injected into the mice. The extent of response observed seems logical given that low numbers of partially differentiated neoislet-like clusters were implanted; given the poor nutrient environment for the grafts due to the high blood glucose levels; and given that mouse cells are far less sensitive to human insulin than mouse insulin. We assume that a normoglycemic state would be achieved within the time frame we used if higher numbers of neoislets were transplanted.