Deep tissue optical 3D imaging reveals preferential preservation of extra-islet β-cells in late-onset Type 1 Diabetes

As residual β-cell function may have positive effects on diabetes regulation in T1D, details on its spatial distribution and mass could provide important information for potential future therapeutic regimens. We implemented an optical 3D imaging pipeline to generate a first account of the 3D-spatial and volumetric distribution of the remaining β-cells throughout the volume of an entire human late onset T1D pancreas at a microscopic resolution. As expected, β-cell mass was dramatically lower than in the non-diabetic pancreas. However, the pancreatic head displayed a morphology and size resembling the non-diabetic pancreas and had a 3 times higher β-cell density compared to the rest of the organ. Surprisingly, only a fraction of the residual β-cells were located within islet structures. Instead, the absolute majority were present as extra-islet β-cells, either as scattered individual cells or as clusters of β-cells, spatially separated from all other endocrine cell-types. Jointly, these extra-islet β-cells appeared roughly 60x less prone to succumb than islet associated β-cells. In sharp contrast to β-cell mass, α-cell density appeared unaffected. This 3D whole organ depiction of an entire long standing, late onset, T1D pancreas shows that individual β-cells may be preserved in a highly regionalized manner, potentially reflecting key aspects of disease dynamics.