Development of cell markers for the identification and expansion of islet progenitor cells

Abstract

Diabetes mellitus results from the anatomical or functional loss of insulin-producing beta cells of the pancreas. Despite significant advances in current treatment, patients with diabetes still do not maintain optimal glucose levels and therefore face debilitating complications such as hypoglycemia, retinopathy or cardiovascular diseases later in life. Islet transplantation therefore holds great promise as an ultimate cure for diabetes. However, the shortage of availability of donor sources of islets for transplantation has largely hampered this therapy. In this respect, the use of alternative sources of islets such as the ex vivo culture and expansion and differentiation of functional endocrine cells for treating diabetes has been a major focus of diabetes research. The identity of the islet stem/progenitor cells has remained either elusive or at least equivocal because of the lack of cell markers for identification of these cells. Recent successes in studying the organogenesis of pancreas as well as in vitro islet progenitor cell identification studies have provided tremendous insight for the cell markers that are essential in the isolation and characterization of these cells prospectively both in vivo and in vitro. If we can identify the markers that will aid the isolation and purification of islet progenitor cells, or factors that determine pancreatic cell fate, we might be able to coerce them from turning into specific endocrine cells or pancreas in vitro. This article will focus on this subject and will review the latest achievements in the study of cell markers for islet progenitor cells.

Combined gastrin and epidermal growth factor treatment induces islet regeneration and restores normoglycaemia in C57Bl6/J mice treated with alloxan

“…According to the literature, different cell types in different models could contribute to regeneration in the pancreas [12]. Our data suggest that in the present model duct cells are involved.…”

Inhibition of Activin Signaling Induces Pancreatic Epithelial Cell Expansion and Diminishes Terminal Differentiation of Pancreatic β-Cells

“…Activin A also induces differentiation of human fetal pancreatic endocrine cells (28). Interestingly, activins are upregulated in duct cells following partial pancreatectomy and streptozotocin injection, suggesting that activins might be involved in the initiation of ␤-cell neogenesis following distinct stimuli in adulthood (18,29). Activins repress the expansion of pancreatic cancer cells, paralleling our observation (30) in the regenerating pancreas.…”

Morphogenetic plasticity of adult human pancreatic islets of Langerhans

“…34,35 However, the existence of a static population of functionally undifferentiated progenitors cells in the adult pancreas remains controversial. 2,[36][37][38][39][40][41] Taken together, various intracellular signaling molecules and transcription factors have been proposed to control the phenotype of tissues in the developing pancreas, but their role in the adult pancreas remains to be confirmed.…”