The pancreatic ductal epithelium serves as a potential pool of progenitor cells

Abstract

With the increasing success of islet transplantation, beta-cell replacement therapy has had renewed interest. To make such a therapy available to more than a few of the thousands of patients with diabetes, new sources of insulin-producing cells must become readily available. The most promising sources are stem cells, whether embryonic or adult stem cells. Clearly identifiable adult pancreatic stem cells have yet to be characterized. Although considerable evidence suggests their possibility, recent lineage-tracing experiments challenge their existence. Even in light of these lineage-tracing experiments, we suggest that evidence for neogenesis or new islet formation after birth remains strong. Our work has suggested that the pancreatic duct epithelium itself serves as a pool for progenitors for both islet and acinar tissues after birth and into adulthood and, thus, that the duct epithelium can be considered 'facultative stem cells'. We will develop our case for this hypothesis in this perspective.

Sustained insulin secretory response in human islets co-cultured with pancreatic duct-derived epithelial cells within a rotational cell culture system

“…The population of ductal cells used in the present investigation has previously been described [21,24,28]. Thus, the expansion of cells derived from the islet-depleted exocrine fraction, which is usually discarded following isolation, has been shown to give rise to a near homogeneous population of CK19-positive epithelial cells, with minimal fibroblast contamination during the initial phase of culture [21,25].…”

“…Thus, the expansion of cells derived from the islet-depleted exocrine fraction, which is usually discarded following isolation, has been shown to give rise to a near homogeneous population of CK19-positive epithelial cells, with minimal fibroblast contamination during the initial phase of culture [21,25]. Although it is not possible to completely eliminate endocrine components from the initial plated material, previous studies have shown that such culture conditions are not conducive either to the adherence or prolonged survival of native islet cells [25] and that any endocrine cells that do exist become de-differentiated within 3-4 days of monolayer culture [24,29].…”

“…The islet-depleted exocrine fraction was washed and plated for culture at high density in T75 flasks as previously described [21,24]. The vast majority (>80%) of the plated material remained non-adherent at 48 h and was discarded in the first medium change.…”

“…In the present investigation we sought to determine whether appropriate glucose signalling and insulin secretion could be restored in culture by re-establishing cellular interactions between islets and non-endocrine components of the human pancreas. Specifically, we aimed to re-introduce the influences exerted by pancreatic ductal epithelial cells (DECs), which are considered to be a potential source of trophic factors [19], ECM components [20] and beta cell progenitors [21] thought to contribute to sustained graft survival following islet transplantation [22].…”

A feat of metabolic proportions: Pdx1 orchestrates islet development and function in the maintenance of glucose homeostasis

“…Activation of Pdx1 in duct cells of the pancreas has also been observed following partial pancreatectomy in mice [85] and in insulin resistant Zucker fatty (ZF) rats [83]. Importantly in this regard, Pdx1 expression is often observed in proliferating duct cells [77,94,95], and such cells have been suggested to serve as substrate for β cell neogenesis, particularly in cases of adaptive hyperplasia or pancreas regeneration [92,[96][97][98][99]. A recent study suggests that Pdx1, in complex with TALE transcription factors, negatively regulates the duct-specific keratin 19 gene in mature duct cells [100].…”