Three-dimensional pancreas organogenesis models

Abstract

A rediscovery of three-dimensional culture has led to the development of organ biogenesis, homeostasis and disease models applicable to human tissues. The so-called organoids that have recently flourished serve as valuable models bridging between cell lines or primary cells grown on the bottom of culture plates and experiments performed in vivo. Though not recapitulating all aspects of organ physiology, the miniature organs generated in a dish are useful models emerging for the pancreas, starting from embryonic progenitors, adult cells, tumour cells and stem cells. This review focusses on the currently available systems and their relevance to the study of the pancreas, of β-cells and of several pancreatic diseases including diabetes. We discuss the expected future developments for studying human pancreas development and function, for developing diabetes models and for producing therapeutic cells.

Keywords: bioengineering; diabetes; disease; modelling; organoids; spheres; spheroids; stem cells; therapy.

Figure 1. Spheres and organoids from embryonic tissues

Embryonic pancreatic progenitors from E10.5 (a) [32]) or E11.5 (b) [29]) mouse embryos are expanded in Matrigel and in presence of the medium components indicated. The expanding cells organize into spheres or organoids. Modified from [74].

Figure 2. Adult spheres and further endocrine differentiation

Spheres forming from mouse and human adenocarcinoma (a) [57] [34], adult murine ducts (b) [39] (c) [38], or human pancreatic ducts (d) [40]), islets (e) [47, 48] or aldefluor-labelled exocrine/terminal duct cells (f) [51]. They are expanded in semisolid matrixes (Matrigel) (a-d) or in suspension on non-adhesive plates (e, f) and generate dense (c) or hollow (a-f) spheres in presence of the soluble factors indicated. Different approaches have been used to generate endocrine cells from these cultures, as indicated. Modified from [74].