5.

(A) Under normal conditions β-cell function is influenced by cell-cell, cell-matrix and systemic interactions. Even after islet transplantation β-cell survival as well as function are maintained and stable for decades (as seen in autotransplantation of islets). Even after transplantation into the liver, islet cyto- architecture is maintained. Therefore, we hypothesize that β-cells either generated in vitro out of stem cells or ex vivo through expansion of progenitor cells might enface the problem of not being fully functional due to the lack of proper cell-cell or cell-matrix interactions. (B) While epithelial cells in the exocrine compartment (shown in brown colour at the left) produce their own basement membrane (see arrow), β-cells in the Islets of Langerhans (appear in red due to dithizone staining) do not (see arrow) [83]. Their basement membrane is produced from the underlying endothelial cells, a fact underlining the above-mentioned hypothesis.