cells. dynamics of adult murine thymidine analog incorporation and radiocarbon dating

cells. dynamics of adult murine thymidine analog incorporation and radiocarbon dating [31]. Remarkably the adaptive increase of are very limited when restricted to primary proliferation of purified human and rat have not been clearly identified. 2.2 Cells Differentiation of endocrine non-cells) resulted in a shift of all endocrine lineages toward a cells (via an intermediate stage of Ngn3 positive Mouse monoclonal to SMN1 cells). However the newly R788 (Fostamatinib) formed cells failed to correct the hypoglucagonemia since they were shown to be rapidly converted into cells. Importantly almost all (~90%) were bihormonal (still expressing glucagon even as far as 10 months after ablation). Of note no cells. Interestingly the authors also observed that under injury conditions cells were able to replicate. However no cells or cells especially if their capacity to replicate under injury condition is confirmed could be an ideal intraislet source for regeneration of were reported to form 3D clusters that differentiate to functional islet cells which are able to respond to a glucose challenge and to reverse diabetes in mice [60]. An interesting strategy for the prospective isolation of putative progenitors from an enriched ductal cell populace is also being pursued by Taniguchi and colleagues [61 62 The approach combines immunohistochemical analysis of mouse pancreas to define new phenotypic markers and flow cytometry cell sorting to isolate clonal cell populations that are able to differentiate toward the endocrine lineage or and to secrete insulin in a glucose-dependent manner [63]. Furthermore Bonner-Weir and collaborators showed that human primary ductal cells could be isolated from islet-depleted pancreatic tissue expanded in culture and brought on to differentiate towards glucose responsive islet-like clusters [64]. These results were confirmed by Gao et al. who further characterized the nature of these pancreatic progenitor cells [65]. During monolayer growth two subpopulations of proliferating cells were observed CK19-positive ductal cells at an early time point (day 3) and nestin-positive cells at a later time point (day 7). Under serum-free conditions and Matrigel covering of the cells the CK19-positive cells but not the Nestin-positive cells were able to form islet-like clusters that contain insulin- and glucagon-positive cells. When transplanted under the kidney capsule of nude mice one out of five grafts exhibited further growth with foci of both endocrine and exocrine cells. Next Bonner-Weir and colleagues used magnetic cell sorting and antibodies raised against the ductal surface marker CA19-9 to isolate ductal cells from islet-depleted tissue [66]. Transplantation experiments of purified ductal cells versus unpurified preparations (56% CK19-positive cells only) into normoglycemic NOD/SCID mice revealed that differentiation of ductal cells to insulin-producing cells was dependent on the presence of nonductal cells probably pancreatic stromal cells as suggested by the authors. Of interest islet-to-duct plasticity has also been reported for human cells [67 68 Although some lineage tracing studies in rodents have provided contradictory results most and data from both human studies indicate that cells from the ductal compartment are an attractive putative cell source for R788 (Fostamatinib) after isolation of acini and identification of putative transitional cells coexpressing acinus-specific (amylase) R788 (Fostamatinib) and lineage tracing analyses using acinus-specific promoters (amylase and elastase). Replication of preexisting acinar cells is seen as the major mechanism for regeneration of the acinar tissue. Moreover acinus-to-duct transdifferentiation has been reported to occur [74]. However the same authors also showed that this insulin positive cells adjacent to acinus-derived ductal cells arose from preexisting insulin-positive cells and not from acinar cells. Along the same line Stoffers and collaborator failed to observe any acinus-to-in pancreas from adult mice was sufficient to induce the transdifferentiation of mature exocrine cells into lineage tracing study using the acinus-specific amylase or elastase promoter confirmed the R788 (Fostamatinib) identity of the starting population. Furthermore acinus-to-duct transdifferentiation was proven to take place in response to EGF-receptor.