Approaches towards endogenous pancreatic regeneration

Abstract

The phenomenon of pancreatic regeneration in mammals has been well documented. It has been shown that pancreatic tissue is able to regenerate in several species of mammal after surgical insult. This tissue is also known to have the potential to maintain or increase its beta-cell mass in response to metabolic demands during pregnancy and obesity. Since deficiency in beta-cell mass is the hallmark of most forms of diabetes, it is worthwhile understanding pancreatic regeneration in the context of this disease. With this view in mind, this article aims to discuss the potential use in clinical strategies of knowledge that we obtained from studies carried out in animal models of diabetes. Approaches to achieve this goal involve the use of biomolecules, adult stem cells and gene therapy. Various molecules, such as glucagon-like peptide-1, beta-cellulin, nicotinamide, gastrin, epidermal growth factor-1 and thyroid hormone, play major roles in the initiation of endogenous islet regeneration in diabetes. The most accepted hypothesis is that these molecules stimulate islet precursor cells to undergo neogenesis or to induce replication of existing beta-cells, emphasizing the importance of pancreas-resident stem/progenitor cells in islet regeneration. Moreover, the potential of adult stem cell population from bone marrow, umbilical cord blood, liver, spleen, or amniotic membrane, is also discussed with regard to their potential to induce pancreatic regeneration.

Figure 1. Possible mechanisms of islet β-cell birth

New β-cells may emerge after injury, apoptosis as a result of inflammation, immune-overreactivity or oxidation, or by exogenous stimuli emanating from different cell sources. Neogenesis may originate from progenitor cells residing within the pancreas. Differentiation may be brought about by different subsets of stem cells. Replication occurs when differentiated pancreatic cells duplicate while transdifferentiation is a process thought to be equipped by undifferentiated progenitors not necessarily preassigned to the pancreas.

Figure 2

Critical balance between accelerating and inhibitory factors affecting adult stem cell expansion and differentiation for triggering pancreatic regeneration.