Partial duct ligation: β-cell proliferation and beyond

Experimentally induced injury is an established strategy for studying mechanisms of tissue remodeling with the final goal to develop new regenerative therapies. Under normal physiological conditions, proliferation and differentiation of progenitor cells, including even canonical stem-cell-like activity, can be stimulated in tissues such as brain and liver that have a low cellular turnover rate. The presence of stem/progenitor cells in the pancreas could be relevant to normal homeostatic maintenance of various cell types in this organ such as endocrine-hormone expressing cells, enzyme-secreting acinar cells, and the less-secretory exocrine duct cells. Further, pancreatic stem/progenitor cells may be a possible source for replenishing cells destroyed by autoimmune disease or other stressors. We speculate that proliferative progenitors might be isolated, expanded, and differentiated in vitro to alleviate the donor scarcity in human islet transplantation and may therefore be developed as a therapy for diabetes. The existence and exact location of adult stem- or progenitor-like cells that can give rise to functional beta cells is, however, highly controversial. This perspective focuses on findings from a severe insult model (PDL: partial duct ligation) with a long history. PDL received renewed attention when Xu et al. (2008) combined it with genetic reporter strategies now possible in mice, to try to identify and isolate cells acting as beta cell progenitors. In vivo beta cell neogenesis under PDL was recently substantiated. Because the outcomes from this technique appear to vary across labs, we summarize and discuss some of the reported discrepancies to help identify current limitations and pitfalls of this model as well as opportunities for forward progress.