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

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

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. Posttransplantation, islets...

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Published in:Journal of biophotonics Vol. 13; no. 12; pp. e202000375 - n/a
Main Authors: Zbinden, Aline, Carvajal Berrio, Daniel A., Urbanczyk, Max, Layland, Shannon L., Bosch, Mariella, Fliri, Sandro, Lu, Chuan‐en, Jeyagaran, Abiramy, Loskill, Peter, Duffy, Garry P., Schenke‐Layland, Katja
Format: Journal Article
Language:English
Published: Weinheim WILEY‐VCH Verlag GmbH & Co. KGaA 01-12-2020
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Subjects:
Basement membranes
Beta cells
Damage
Diabetes mellitus
Diabetes mellitus (insulin dependent)
FLIM
Fluorescence
Graft rejection
Grafts
Heterogeneity
Hypoxia
Insulin
Islet cells
Metabolism
Pancreas
pancreatic islet
Pancreatic islet transplantation
Quality assessment
Transplantation
type 1 diabetes
hypoxia
pancreatic islet
type 1 diabetes
FLIM
insulin
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Summary: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. 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 β‐cells in a three‐dimensional in vitro model (= pseudo‐islets). We demonstrate how (pre‐) hypoxic β‐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 β‐cell islet transplantation. Fluorescence lifetime imaging microscopy (FLIM) is a powerful technique for the screening of pancreatic β‐cell‐composed islets prior transplantation. In our study, FLIM‐based metabolic profiles utilizing the endogenous fluorescence of the coenzymes nicotinamide adenine dinucleotide and flavin adenine dinucleotide enabled the detection of early hypoxia‐induced damages. Glucose‐response was detected noninvasively in β‐cells. The use of FLIM has the potential to improve the outcome of β‐cell islet transplantation to treat type 1 diabetes mellitus.
Bibliography:Funding information
Aline Zbinden and Daniel A. Carvajal Berrio contributed equally to this study.
Deutsche Forschungsgemeinschaft, Grant/Award Number: INST 2388/33‐1; Horizon 2020 Framework Programme, Grant/Award Numbers: H2020‐ITN 766181, H2020‐NMP10‐2014‐645991‐2; International Foundation for Ethical Research; Ministry of Science, Research and the Arts of Baden‐Württemberg, Grant/Award Numbers: 33‐729.55‐3/214, SI‐BW 01222‐91
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ISSN:1864-063X
1864-0648
DOI:10.1002/jbio.202000375