Expansion and redifferentiation of adult human pancreatic islet cells

Dose-dependent requirement of patched homologue 1 in mouse pancreatic beta cell mass

“…While two studies have suggested that under certain conditions pancreatic beta cells can undergo EMT into fibroblast-like cells under culture [32,33], a recent study used lineage tracing to demonstrate that islet-derived fibroblast-like cells were not EMT-derived [34]. The increased pancreatic mesenchyme observed in our Ptch1 mutants resembled an EMT event.…”

“…Thus, increased HH signalling results in a reduction of the pancreatic epithelial cells. On the other hand, no studies have investigated the possibility that the increased mesenchyme is formed by an epithelial to mesenchymal transition (EMT) in pancreas of Ptch1 mutants [32][33][34]. To investigate whether the increased mesenchymal cells are indeed the result of an EMT, we performed Cre-lox recombination studies based on in vivo genetic lineage tracing.…”

Epithelial-to-mesenchymal transition in pancreatic islet β cells

“…Generation of mesenchymal-like progenitor cells from β cells was also reported shortly after this initial presentation. 5 In this study, single cells obtained from human islets were cultured in vitro and Pdx1 producing human β cells were seen to co-express mesenchymal proteins during expansion, thus suggesting β-cell origin of mesenchymal progenitors. 5 hIPCs are proposed to be better precursors 6 since they are derived from β cells and therefore would inherit epigenetic marks that define an active insulin promoter region.…”

“…5 In this study, single cells obtained from human islets were cultured in vitro and Pdx1 producing human β cells were seen to co-express mesenchymal proteins during expansion, thus suggesting β-cell origin of mesenchymal progenitors. 5 hIPCs are proposed to be better precursors 6 since they are derived from β cells and therefore would inherit epigenetic marks that define an active insulin promoter region. Later on it was confirmed that insulin promoter region in hIPCs retain open chromatin conformation after expansion in vitro 7,8 and hence can be differentiated into insulin-producing cells in vitro 4,5 or in vivo.…”

In vitro expansion of human beta cells

“…Evidence supports the regeneration of adult mouse beta cells in vivo from both insulin-producing cells [1,2] and pancreatic duct cells [3], and recent analyses of autopsied human pancreatic tissue suggest that human islets may grow by beta cell replication [4]. However, assessment of beta cell proliferation in vitro is much harder, since the beta cell phenotype is rapidly lost [5,6], making it difficult to determine whether the loss of beta cell markers in the expanded cells reflects beta cell dedifferentiation, or beta cell death accompanied by expansion of pancreatic cells from a non-beta cell origin. In genetic lineage-tracing studies using islets from transgenic mice, the specific labelling of beta cells with a fluorescent protein produced under the control of an ubiquitous promoter allowed tracking of mouse beta cell fate in vitro [7].…”