Concise review: in search of unlimited sources of functional human pancreatic beta cells

Abstract

It is well-established that insulin-producing pancreatic beta cells are central in diabetes. In type 1 diabetes, beta cells are destroyed by an autoimmune mechanism, whereas in type 2 diabetes, there is a decrease in functional beta-cell mass. In this context, studying beta cells is of major importance. Beta cells represent only 1% of total pancreatic cells and are found dispersed in the pancreatic gland. During the past decades, many tools and approaches have been developed to study rodent beta cells that efficiently pushed the field forward. However, rodent and human beta cells are not identical, and our knowledge of human beta cells has not progressed as quickly as our understanding of rodent beta cells. We believe that one of the reasons for this inefficient progress is the difficulty of accessing unlimited sources of functional human pancreatic beta cells. The main focus of this review concerns recent strategies to generate new sources of human pancreatic beta cells.

Figure 1.

Comparative organization of endocrine cells in rat and human islets. Pancreatic sections from adult rat (A) and human (B) pancreases were immunostained with antibodies against insulin (red) and glucagon (green). The nuclei were stained with Hoechst 33342 fluorescent stain (blue). Note that in rat islets, glucagon-positive cells surround insulin-positive cells, which is not the case in human islets. Scale bars = 12.5 μm.

Figure 2.

Schematic analysis of the procedure recently used to generate beta cells from human fetal pancreases [1]. Immature human fetal pancreases were transduced with lentiviral vectors that expressed SV40T under the control of the insulin promoter. Transduced pancreases were next transplanted under the kidney capsule of immunoincompetent SCID mice where insulinomas developed, from which human beta-cell lines were derived. Abbreviations: LTR, long terminal repeat; Ins, insulin; SV40T, large-T antigen of simian virus 40.