β-Cell Generation: Can Rodent Studies Be Translated to Humans?

Abstract

β-cell replacement by allogeneic islet transplantation is a promising approach for patients with type 1 diabetes, but the shortage of organ donors requires new sources of β cells. Islet regeneration in vivo and generation of β-cells ex vivo followed by transplantation represent attractive therapeutic alternatives to restore the β-cell mass. In this paper, we discuss different postnatal cell types that have been envisaged as potential sources for future β-cell replacement therapy. The ultimate goal being translation to the clinic, a particular attention is given to the discrepancies between findings from studies performed in rodents (both ex vivo on primary cells and in vivo on animal models), when compared with clinical data and studies performed on human cells.

Figure 1

Section of murine pancreas stained with anti-insulin (red) and anti-BrdU (brown) antibodies. C57BL/6 mice were on a high-fat diet for 6 weeks. BrdU was injected for one week by s.c. injections, thereby labeling all proliferating cells. A number of replicating β-cells (arrows) and acinar cells are detected.

Figure 2

Section of human pancreatic exocrine tissue stained with an anti-insulin antibody (red). Nuclei are stained by DAPI (blue). An insulin-positive cell (arrow) is detected in the duct lining suggesting a process of β-cell neogenesis.