Islets-on-Chip: A Tool for Real-Time Assessment of Islet Function Prior to Transplantation
Résumé
Islet transplantation improves metabolic control in patients with unstable type 1 diabetes. Clinical outcomes have been improving over the last decade, and the widely used beta-score allows the evaluation of transplantation results. However, predictive pre-transplantation criteria of islet quality for clinical outcomes are lacking. In this proof-of-concept study, we examined whether characterization of the electrical activity of donor islets could provide a criterion. Aliquots of 8 human donor islets from the STABILOT study, sampled from islet preparations before transplantation, were characterized for purity and split for glucose-induced insulin secretion and electrical activity using multi-electrode-arrays. The latter tests glucose concentration dependencies, biphasic activity, hormones, and drug effects (adrenalin, GLP-1, glibenclamide) and provides a ranking of CHIP-scores from 1 to 6 (best) based on electrical islet activity. The analysis was performed online in real time using a dedicated board or offline. Grouping of beta-scores and CHIP-scores with high, intermediate, and low values was observed. Further analysis indicated correlation between CHIP-score and beta-score, although significance was not attained (R = 0.51, p = 0.1). This novel approach is easily implantable in islet isolation units and might provide means for the prediction of clinical outcomes. We acknowledge the small cohort size as the limitation of this pilot study.
Mots clés
islet transplantation
transplant assessment
electrophysiology
diabetes mellitus
islet
multielectrode array cAMP
cyclic AMP GLP-1
Glucagon-like peptide 1 GSIS
Glucose-induced insulin secretion HbA 1c
Glycated hemoglobin MEA
Multielectrode array SP
Slow potentials
cyclic AMP
GLP-1
Glucagon-like peptide 1
GSIS
Glucose-induced insulin secretion
HbA 1c
Glycated hemoglobin
MEA
Multielectrode array
SP
Domaines
Sciences du Vivant [q-bio]
Fichier principal
2022 Advanced Science - Vertical Organic Electrochemical Transistors and Electronics for Low Amplitude.pdf (6.23 Mo)
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2022 Towards the Integration of an Islet-Based Biosensor in Closed-Loop Therapies for Patients With Type 1 Diabetes.pdf (12.31 Mo)
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2023 Islet-on-Chip.pdf (1.72 Mo)
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