Fig. 3. Organoid systems of different complexity, enabling interactions between cells and organs in the course of diabetes mellitus to be studied.

Different 3D culture models exist for monogenic diabetes mellitus, type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). The figure outlines the challenges associated with modelling these diseases and the assays that are available for each system. Simple epithelial pancreas organoid models for neonatal diabetes mellitus and maturity-onset diabetes of the young (MODY) are available. These models can be composed of either progenitors and endocrine cells or aggregated pluripotent stem cell-derived endocrine cells alone. Co-culture of epithelial cells with mesenchyme and/or endothelial cells to form blood vessels is possible but difficult to stabilize and has not yet been achieved with pancreatic mesenchyme and endothelial cells. The maturity of the cells corresponds to embryonic cells and so can be problematic for modelling monogenic diabetes mellitus. The first models for the study of T1DM and T2DM are emerging. These models combine pancreatic organoids with immune cells or organoids from other metabolic organs for the study of T1DM and T2DM, respectively.