Predicting the function of islets after transplantation

Darden, Carly M.; Farrow, Anne Elizabeth; Rajan, Shanthini Kuduva; Lakhani, Muhaib; Lawrence, Michael C.; Naziruddin, Bashoo

doi:10.1016/b978-0-12-814833-4.00044-7

Cited by 5 publications

(5 citation statements)

References 54 publications

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“…Quantifying βcell death has been evaluated as a predictor of graft function in ITx, however, correlations are low-to-moderate and long-term outcomes remain underreported. [34][35][36] Further studies will focus on identifying patient-related, isolation/procurement-related, and immune-related factors to generate composite predictive tools to establish more realistic expectations with current and future β-cell replacement therapies.…”

Section: Discussionmentioning

confidence: 99%

“…These could be driven by the nature and degree of cell death pre-transplant and peritransplant (ie, islet isolation/culture vs. warm/cold ischemia), and post-transplant (ie, hypoxia due to delayed revascularization vs. ischemia-reperfusion injury). Quantifying β-cell death has been evaluated as a predictor of graft function in ITx, however, correlations are low-to-moderate and long-term outcomes remain underreported 34–36. Further studies will focus on identifying patient-related, isolation/procurement-related, and immune-related factors to generate composite predictive tools to establish more realistic expectations with current and future β-cell replacement therapies.…”

Section: Discussionmentioning

confidence: 99%

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Pancreas and Islet Transplantation: Comparative Outcome Analysis of a Single-centre Cohort Over 20-years

et al. 2022

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Objective: To provide the largest single-center analysis of islet (ITx) and pancreas (PTx) transplantation. Summary Background Data: Studies describing long-term outcomes with ITx and PTx are scarce. Methods: We included adults undergoing ITx (n = 266) and PTx (n = 146) at the University of Alberta from January 1999 to October 2019. Outcomes include patient and graft survival, insulin independence, glycemic control, procedure-related complications, and hospital readmissions. Data are presented as medians (interquartile ranges, IQR) and absolute numbers (percentages, %) and compared using Mann-Whitney and χ 2 tests. Kaplan-Meier estimates, Cox proportional hazard models and mixed main effects models were implemented. Results: Crude mortality was 9.4% and 14.4% after ITx and PTx, respectively (P = 0.141). Sex-adjusted and age-adjusted hazard-ratio for mortality was 2.08 (95% CI, 1.04-4.17, P = 0.038) for PTx versus ITx. Insulin independence occurred in 78.6% and 92.5% in ITx and PTx recipients, respectively (P = 0.0003), while the total duration of insulin independence was 2.1 (IQR 0.8-4.6) and 6.7 (IQR 2.9-12.4) year for ITx and PTx, respectively (P = 2.2×10 -22 ). Graft failure ensued in 34.2% and 19.9% after ITx and PTx, respectively (P = 0.002). Glycemic control improved for up to 20-years post-transplant, particularly for PTx recipients (group, P = 7.4×10 -7 , time, P = 4.8×10 -6 , group*time, P = 1.2×10 -7 ). Procedure-related complications and hospital readmissions were higher after PTx (P = 2.5×10 -32 and P = 6.4×10 -112 , respectively). Conclusions: PTx shows higher sex-adjusted and age-adjusted mortality, procedure-related complications and readmissions compared with ITx. Conversely, insulin independence, graft survival and glycemic control are better with PTx. This study provides data to balance risks and benefits with ITx and PTx, which could improve shared decision-making.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pancreas and Islet Transplantation: Comparative Outcome Analysis of a Single-centre Cohort Over 20-years

et al. 2022

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“…Since the role of insulin is fundamental in lipid and lipoprotein homeostasis, metabolomics-based studies have been undertaken to understand the effect of IR on PAH pathobiology and its impact on clinical outcomes. 114,115 To assess b-cell function, insulin sensitivity and nutrient metabolism in PAH patients, Mey et al (2019) used a hyperglycaemic clamp procedure, which is considered the gold standard 116 in assessing insulin secretion along with plasma metabolomics. 115 It was observed that while the pancreatic b-cell did not show any changes in insulin secretion, there was an unexpected increase in insulin sensitivity in skeletal muscles of PAH patients and a metabolic shift towards utilization of ketones and lipids.…”

Section: Metabolomics In Phmentioning

confidence: 99%

Understanding pulmonary hypertension: the need for an integrative metabolomics and transcriptomics approach

Choudhury,

Dasgupta,

Bhattacharyya

et al. 2024

Mol. Omics

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“…Islet graft function and survival after transplantation are commonly assessed by glucose tolerance tests, C-peptide and hemoglobin A1c levels, exogenous insulin usage, and noninvasive imaging techniques ( 20 , 21 ). However, these assessments tend to reflect the loss of islet function, offering little insight into islet stress, islet engraftment, and the ongoing loss of islet function.…”

Section: Introductionmentioning

confidence: 99%

Role of Exosomes in Islet Transplantation

et al. 2021

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Exosomes are known for their ability to transport nucleic acid, lipid, and protein molecules, which allows for communication between cells and tissues. The cargo of the exosomes can have a variety of effects on a wide range of targets to mediate biological function. Pancreatic islet transplantation is a minimally invasive cell replacement therapy to prevent or reverse diabetes mellitus and is currently performed in patients with uncontrolled type 1 diabetes or chronic pancreatitis. Exosomes have become a focus in the field of islet transplantation for the study of diagnostic markers of islet cell viability and function. A growing list of miRNAs identified from exosomes collected during the process of isolating islets can be used as diagnostic biomarkers of islet stress and damage, leading to a better understanding of critical steps of the isolation procedure that can be improved to increase islet yield and quality. Exosomes have also been implicated as a possible contributor to islet graft rejection following transplantation, as they carry donor major histocompatibility complex molecules, which are then processed by recipient antigen-presenting cells and sensed by the recipient immune cells. Exosomes may find their way into the therapeutic realm of islet transplantation, as exosomes isolated from mesenchymal stem cells have shown promising results in early studies that have seen increased viability and functionality of isolated and grafted islets in vitro as well as in vivo. With the study of exosomes still in its infancy, continued research on the role of exosomes in islet transplantation will be paramount to understanding beta cell regeneration and improving long-term graft function.

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Predicting the function of islets after transplantation

Cited by 5 publications

References 54 publications

Pancreas and Islet Transplantation: Comparative Outcome Analysis of a Single-centre Cohort Over 20-years

Pancreas and Islet Transplantation: Comparative Outcome Analysis of a Single-centre Cohort Over 20-years

Understanding pulmonary hypertension: the need for an integrative metabolomics and transcriptomics approach

Role of Exosomes in Islet Transplantation

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