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Fluorescence lifetime metabolic mapping of hypoxia-induced damage in pancreatic pseudo-islets.

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Pancreatic islet isolation from donor pancreases is an essential step for the transplantation of insulin-secreting β-cells as a therapy to treat type 1 diabetes mellitus. This process however damages islet… Click to show full abstract

Pancreatic islet isolation from donor pancreases is an essential step for the transplantation of insulin-secreting β-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. Post-transplantation, 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 do 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 non-invasively assess the viability and functionality of pancreatic β-cells in a 3-dimensional in vitro model (pseudo-islets). We demonstrate how (pre-) hypoxic β-cell-composed pseudo-islets can be discriminated from healthy functional pseudo-islets based on their FLIM-based metabolic profiles. The use of FLIM during the pre-transplantation pancreatic islet selection process has the potential to improve the outcome of β-cell islet transplantation. This article is protected by copyright. All rights reserved.

Keywords: islet; pseudo islets; transplantation; lifetime metabolic; fluorescence lifetime

Journal Title: Journal of biophotonics
Year Published: 2020

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