Zbinden, A.A.ZbindenCarvajal Berrio, D.A.D.A.Carvajal BerrioUrbanczyk, M.M.UrbanczykLayland, ShannonShannonLaylandBosch, M.M.BoschFliri, S.S.FliriLu, C.-E.C.-E.LuJeyagaran, A.A.JeyagaranLoskill, P.P.LoskillDuffy, G.P.G.P.DuffySchenke-Layland, KatjaKatjaSchenke-Layland2022-03-062022-03-062020https://publica.fraunhofer.de/handle/publica/26551410.1002/jbio.202000375Pancreatic islet isolation from donor pancreases is an essential step for the transplantation of insulin-secreting v-cells as a therapy to treat type 1 diabetes mellitus. This process however damages islet basement membranes, which can lead to islet dysfunction or death. Posttransplantation, islets are further stressed by a hypoxic environment and immune reactions that cause poor engraftment and graft failure. The current standards to assess islet quality before transplantation are destructive procedures, performed on a small islet population that does not reflect the heterogeneity of large isolated islet batches. In this study, we incorporated fluorescence lifetime imaging microscopy (FLIM) into a pancreas-on-chip system to establish a protocol to noninvasively assess the viability and functionality of pancreatic v-cells in a three-dimensional in vitro model (= pseudo-islets). We demonstrate how (pre-) hypoxic v-cell-composed pseudo-islets can be discriminated from healthy functional pseudo-islets according to their FLIM-based metabolic profiles. The use of FLIM during the pretransplantation pancreatic islet selection process has the potential to improve the outcome of v-cell islet transplantation.en660570610620journal article