Association between primary graft function and 5-year outcomes of islet allogeneic transplantation in type 1 diabetes: a retrospective, multicentre, observational cohort study in 1210 patients from the Collaborative Islet Transplant Registry

Chetboun, Mikaël; Drumez, Élodie; Ballou, Cassandra M.; Maanaoui, Mehdi; Payne, Elizabeth H.; Barton, Franca B.; Kerr–Conte, Julie; Labreuche, Julien; Alejandro, Rodolfo; Aull, M; Bellin, Melena D.; Berney, Thierry; Borja-Cacho, D; Brayman, Kenneth L.; Cagliero, Enrico; Caïazzo, Robert; Cattral, Mark S.; Coates, Toby; Danielson, Kirstie K.; Defrance, F.; Koning, E De; Desai, Chintan S.; Desai, Niraj M.; Gaber, A. Osama; Gmyr, Valéry; Gores, P. F.; Goss, John A.; Gottllieb, P; Greenbaum, Carla J.; Hardy, Mark A.; Harlan, David M.; Hering, Bernhard J.; Kandeel, Fouad; Kaufman, Dixon B.; Kay, Thomas W. H.; Keymeulen, Bart; Khan, Khalid; Kudva, Yogish C.; Larsen, Christian; Mapihan, Kristell Le; Levy, G; Levy, Marlon F.; Loudovaris, Thomas; Lundgren, Torbjörn; Maffi, Paola; Markmann, James F.; Marks, W H; Naji, Ali; O’Connell, Philip J.; Oberholzer, José; Odorico, Jon S.; Onaca, Nicholas; Pattou, François; Piemonti, Lorenzo; Pipeleers, Danny; Posselt, Andrew M.; Rajab, Amer; Raverdy, Violeta; Rickels, Michael R.; Ricordi, Camillo; Rossini, A A; Saudek, František; Schrope, Beth; Secchi, Antonio; Senior, Peter; Shapiro, A.M. James; Shaw, James; Stock, Peter G.; Thomas, Diego Sánchez; Thompson, Matthew; Vantyghem, Marie-Christine; Vargas, L; Wang, H; Wiseman, Anthony; Witkowski, Piotr; Yoon, Kun‐Ho

doi:10.1016/s2213-8587(23)00082-7

Cited by 23 publications

(28 citation statements)

References 30 publications

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“…As the physiological tests estimating the hormone content and secretion of human islets in vitro are highly dependent on the experimental conditions and thus challenging to compare between laboratories, mapping and comparing the islet profiles at the protein level offers a more stringent alternative, alone or combined with other islet functionality parameters. In this respect, a very recent and comprehensive study by Chetboun et al developed a model able to predict with reasonable accuracy the clinical long‐term outcome of islet transplantation, employing a validated composite index of islet function based on physiological parameters such as stimulated serum C‐peptide and fasting blood glucose among others 42 . Moreover, the results of this study also point at the importance of evaluating early islet graft functionality.…”

Section: Discussionmentioning

confidence: 71%

Global proteomics reveals insulin abundance as a marker of human islet homeostasis alterations

Mathisen,

Abadpour,

Legøy

et al. 2023

Acta Physiologica

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AimThe variation in quality between the human islet samples represents a major problem for research, especially when used as control material. The assays assessing the quality of human islets used in research are non‐standardized and limited, with many important parameters not being consistently assessed. High‐throughput studies aimed at characterizing the diversity and segregation markers among apparently functionally healthy islet preps are thus a requirement. Here, we designed a pilot study to comprehensively identify the diversity of global proteome signatures and the deviation from normal homeostasis in randomly selected human‐isolated islet samples.MethodsBy using Tandem Mass Tag 16‐plex proteomics, we focused on the recurrently observed disparity in the detected insulin abundance between the samples, used it as a segregating parameter, and analyzed the correlated changes in the proteome signature and homeostasis by pathway analysis.ResultsIn this pilot study, we showed that insulin protein abundance is a predictor of human islet homeostasis and quality. This parameter is independent of other quality predictors within their acceptable range, thus being able to further stratify islets samples of apparent good quality. Human islets with low amounts of insulin displayed changes in their metabolic and signaling profile, especially in regard to energy homeostasis and cell identity maintenance. We further showed that xenotransplantation into diabetic hosts is not expected to improve the pre‐transplantation signature, as it has a negative effect on energy balance, antioxidant activity, and islet cell identity.ConclusionsInsulin protein abundance predicts significant changes in human islet homeostasis among random samples of apparently good quality.

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Section: Discussionmentioning

confidence: 71%

Global proteomics reveals insulin abundance as a marker of human islet homeostasis alterations

Mathisen,

Abadpour,

Legøy

et al. 2023

Acta Physiologica

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“…Transplantation of autologous human islets is considered a therapeutic option for the palliative treatment of chronic pain in people undergoing total pancreatectomy 44 45. Transplantation of human islets obtained from allogeneic, cadaveric pancreata has shown remarkable impact in restoring metabolic control in people with brittle type 1 diabetes worldwide 46. Moreover, with the advent of increasingly unlimited supplies of islets from xenogeneic sources (eg, porcine) and human SC-β having consistent and reproducible ‘donor’ characteristics, dimensions and cytoarchitecture, it will likely be less challenging to develop reliable pretransplant potency assays.…”

Section: Discussionmentioning

confidence: 99%

A static glucose-stimulated insulin secretion (sGSIS) assay that is significantly predictive of time to diabetes reversal in the human islet bioassay

Molano,

Pileggi,

Tse

et al. 2024

BMJ Open Diab Res Care

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IntroductionStatic incubation (static glucose-stimulated insulin secretion, sGSIS) is a measure of islet secretory function. The Stimulation Index (SI; insulin produced in high glucose/insulin produced in low glucose) is currently used as a product release criterion of islet transplant potency.Research design and methodsOur hypothesis was that the Delta, insulin secreted in high glucose minus insulin secreted in low glucose, would be more predictive. To evaluate this hypothesis, sGSIS was performed on 32 consecutive human islet preparations, immobilizing the islets in a slurry of Sepharose beads to minimize mechanical perturbation. Simultaneous full-mass subrenal capsular transplants were performed in chemically induced diabetic immunodeficient mice. Logistic regression analysis was used to determine optimal cut-points for diabetes reversal time and the Fisher Exact Test was used to assess the ability of the Delta and the SI to accurately classify transplant outcomes. Receiver operating characteristic curve analysis was performed on cut-point grouped data, assessing the predictive power and optimal cut-point for each sGSIS potency metric. Finally, standard Kaplan-Meier-type survival analysis was conducted.ResultsIn the case of the sGSIS the Delta provided a superior islet potency metric relative to the SI.ConclusionsThe sGSIS Delta value is predicitive of time to diabetes reversal in the full mass human islet transplant bioassay.

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“…Although exogenous insulin supply alleviates blood glucose levels temporally, the need for frequent injections causes huge burdens and severe adverse complications may occur [2][3][4]. As an alternative strategy that recapitulates endogenous insulin secretion, islet transplantation is promising for long-term glycemic control [5,6]. However, the donor shortage and the required chronic immunosuppression in the islet transplantation pose great challenges in the DM therapeutics [7].…”

Section: Introductionmentioning

confidence: 99%

Biomimetic artificial islet model with vascularized microcapsule structures for durable glycemic control

Li,

Fang,

et al. 2024

Mater. Futures

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Islet transplantation is a promising strategy for diabetes mellitus treatment as it can recapitulate endogenous insulin secretion and provide long-term glycemic control. Islet models constructed in biomaterial scaffolds that reproduce biological characteristics of native islets is a feasible option to circumvent the dilemma of donor shortage and the requirement of chronic immunosuppression. Herein, we developed bioinspired artificial microcapsule-based islet models with microvessels for glycemic control using microfluidic electrospray strategy. Microfluidic electrospray can generate uniform hydrogel microcapsules with core-shell structure for encapsulating islet cells. The cell-laden microcapsules enabled the efficient transportation of nutrient, oxygen, and insulin; as well as the incorporation with microvessels for prompting glucose responsiveness and molecular exchange. We demonstrated by in vivo experiments that the blood glucose, food intake, and body weight of diabetic mouse models were alleviated, and the glucose tolerance was promoted after the engraftment of islet microcapsules. We further demonstrated the improved functionality of transplanted islet model in insulin secretion, immune escape, and microcirculation using standard histological and molecular analysis. These results indicated that the microcapsules with microvessels are promising artificial islet models and are valuable for treating diabetes.

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Association between primary graft function and 5-year outcomes of islet allogeneic transplantation in type 1 diabetes: a retrospective, multicentre, observational cohort study in 1210 patients from the Collaborative Islet Transplant Registry

Cited by 23 publications

References 30 publications

Global proteomics reveals insulin abundance as a marker of human islet homeostasis alterations

Global proteomics reveals insulin abundance as a marker of human islet homeostasis alterations

A static glucose-stimulated insulin secretion (sGSIS) assay that is significantly predictive of time to diabetes reversal in the human islet bioassay

Biomimetic artificial islet model with vascularized microcapsule structures for durable glycemic control

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