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Journal ArticleDOI

Variables in organ donors that affect the recovery of human islets of Langerhans.

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TLDR
In an attempt to reduce the variability in the yields of human islet isolations and to identify donor factors that were potentially deleterious, retrospectively reviewed 153 human islets isolations in the center over a 3-year period suggests an improved approach to the prediction of successful islet isolation from human pancreases.
Abstract
In an attempt to reduce the variability in the yields of human islets isolations and to identify donor factors that were potentially deleterious, we retrospectively reviewed 153 human islets isolations in our center over a 3-year period. Isolations were performed using controlled collagenase perfusion via the duct, automated dissociation, and Ficoll purification. Factors leading to successful isolations (recovery of >100,000 islet equivalents at a purity >50%) were analyzed retrospectively using univariate and multivariate analysis. Critical factors in the multiorgan cadaveric donors that were identified using univariate analysis included donor age (P 15 min) requiring high vasopressors (>15 microgram/kg/min dopamine or >5 microgram/kg/min Levophed) (P>0.01). Independent analysis of 19 donor variables using multivariate logistic stepwise regression showed six factors were statistically significant. Odds ratio (OR) showed that donor age (OR 1.1, P 10 mmol/L) (OR 0.63, P 50-year-old donor group was significantly reduced as compared with the 2.5- to 18-year-old group (P<0.02). Multiple regression analysis using postdigestion and postpurification islet recovery as outcome variables identified BMI, procurement team, pancreas weight, and collagenase digestion time factors tht can affect the recovery of human islets. Locally procured pancreases and donors with elevated minimum blood glucose levels were identified as factors that affect the insulin secretory capabilities of the isolated islets. This review of parameters suggests an improved approach to the prediction of successful islet isolation from human pancreases. Selection of suitable pancreases for processing may improve consistency in human islet isolation and thereby decrease costs.

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Journal ArticleDOI

Islet Transplantation in Seven Patients with Type 1 Diabetes Mellitus Using a Glucocorticoid-Free Immunosuppressive Regimen

TL;DR: The observations in patients with type 1 diabetes indicate that islet transplantation can result in insulin independence with excellent metabolic control when glucocorticoid-free immunosuppression is combined with the infusion of an adequate islet mass.
Journal ArticleDOI

Clinical pancreatic islet transplantation.

TL;DR: The techniques required for human islet isolation, in vitro culture before the transplant and clinical islet transplantation are outlined and the potential risks, long-term outcomes and advances in treatment after the transplant are discussed to further move this treatment towards becoming a more widely available option for patients with type 1 diabetes mellitus and eventually a potential cure.
Journal ArticleDOI

Single-cell transcriptomics of the human endocrine pancreas

TL;DR: It is shown that α- and β-cells from children exhibit less well-defined gene signatures than those in adults, and a robust computational biology framework for cell type annotation is developed, which provides a stepping stone for future explorations of cellular heterogeneity in pancreatic endocrine cells.
Journal ArticleDOI

Superiority of Small Islets in Human Islet Transplantation

TL;DR: Evidence is provided that small islets are superior to large islets with regard to in vitro insulin secretion and show a higher survival rate during both normoxic and hypoxic culture.
Journal ArticleDOI

Refinement of the automated method for human islet isolation and presentation of a closed system for in vitro islet culture.

TL;DR: A standardized technique of islet isolation is presented applying novel means to improve enzymatic digestion and to meet cGMP standards to enhance enzyme digestion and minimize mechanical forces during the digestion process.
References
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Journal ArticleDOI

Immunoassay of Insulin: Two Antibody System: Plasma Insulin Levels of Normal, Subdiabetic and Diabetic Rats

Carl R Morgan, +1 more
- 01 Mar 1963 - 
TL;DR: A two antibody system of insulin assay for immunoassay of insulin induces the production of specific nonprecipitating antibodies, both in experimental animals and in humans.
Journal ArticleDOI

Automated Method for Isolation of Human Pancreatic Islets

TL;DR: An automated method for the isolation of human pancreatic islets meets the following requirements: minimal traumatic action on the islets, continuous digestion in which the islet that are progressively liberated can be saved from further enzymatic action, high yield and purity of the isolated islets.
Journal ArticleDOI

Insulin independence after islet transplantation into type I diabetic patient

TL;DR: The first type I diabetic patient with an established kidney transplant on basal cyclosporin immunosuppression who was able to eliminate the insulin requirement after human islet transplantation into the portal vein is reported, representing the first essential step required to determine the feasibility of islet transplants by future clinical trials.
Journal ArticleDOI

Perifusion of Isolated Rat Islets in Vitro: Participation of the Microtubular System in the Biphasic Release of Insulin

TL;DR: Findings indicate that the microtubular system is involved in both phases of insulin secretion, and the first phase of secretion may be due to the release of beta granules already associated with the micro Tubular system and the second phase could be the result of stored and newlysynthesized granules becoming associatedWith the system.
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