Parameters favouring successful adult pig islet isolations for xenotransplantation in pig‐to‐primate models

Dufrane, Denis; D’Hoore, William; Goebbels, Rose-Marie; Saliez, Alain; Guiot, Yves; Gianello, Pierre

doi:10.1111/j.1399-3089.2006.00275.x

Cited by 67 publications

(76 citation statements)

References 22 publications

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“…We initially speculated that histomorphometric variables assoµm in diameter) indeed predicted in vivo potency, in contrast to the previously suggested quantitative histociated with large islets might be inversely associated with in vivo islet potency because it has been proposed morphometrical parameter of total islet number (4). Another previously suggested quantitative parameter (4), that small islets have better in vivo potency than large the proportion of large islets (>100 µm in diameter), was lation confirmation of islet function was warranted to evaluate damage induced by the isolation process. Therethe most precise predictor of in vivo islet potency, rather than a predictor of islet yield.…”

Section: Test For Predicting Posttransplant In Vivo Islet Potency a Hmentioning

confidence: 99%

“…By contrast, a retPrediction of islet yield and posttransplant outcome in advance of islet transplantation is essential for the rospective study suggested that the total number of islets and the proportion of large islets (>100 µm in diameter) clinical application of porcine islet xenotransplantation. Although several histomorphometric parameters of biopmay be useful quantitative parameters (4). However, this finding needs to be confirmed because only 18 pancresied porcine pancreases have been reported to predict islet yield, variation inherent to the qualitative nature of ases were evaluated.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced Prediction of Porcine Islet Yield and Posttransplant Outcome Using a Combination of Quantitative Histomorphometric Parameters and Flow Cytometry

et al. 2010

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Prediction of islet yield and posttransplant outcome is essential for clinical porcine islet xenotransplantation. Although several histomorphometric parameters of biopsied porcine pancreases are predictive of islet yield, their role in the prediction of in vivo islet potency is unknown. We investigated which histomorphometrical parameter best predicts islet yield and function, and determined whether it enhanced the predictive value of in vitro islet function tests for the prediction of posttransplant outcome. We analyzed the histomorphometry of pancreases from which 60 adult pig islet isolations were obtained. Islet function was assessed using the β-cell viability index based on flow cytometry analysis, oxygen consumption rate, ADP/ATP ratio, and/or concurrent transplantation into NOD/SCID mice. Receiver operating characteristic (ROC) analysis revealed that only islet equivalent (IEQ)/cm 2 and the number of islets >200 µm in diameter significantly predicted an islet yield of >2000 IEQ/g ( p < 0.001 for both) and in vivo islet potency ( p = 0.024 and p = 0.019, respectively). Although not predictive of islet yield, a high proportion of large islets (>100 µm in diameter) best predicted diabetes reversal ( p = 0.001). Multiple regression analysis revealed that the β-cell viability index ( p = 0.003) and the proportion of islets >100 µm in diameter ( p = 0.048) independently predicted mean posttransplant blood glucose level (BGL). When BGL was estimated using both these parameters [area under the ROC curve (AUC), 0.868; 95% confidence interval (CI), 0.730-1.006], it predicted posttransplant outcome more accurately than the β-cell viability index alone (AUC, 0.742; 95% CI, 0.544-0.939). In conclusion, we identified the best histomorphometric predictors of islet yield and posttransplant outcome. This further enhanced the predictive value of the flow cytometry analysis. These parameters should be useful for predicting islet yield and in vivo potency before clinical adult porcine islet xenotransplantation.

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Section: Test For Predicting Posttransplant In Vivo Islet Potency a Hmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enhanced Prediction of Porcine Islet Yield and Posttransplant Outcome Using a Combination of Quantitative Histomorphometric Parameters and Flow Cytometry

et al. 2010

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“…Dufrane D's group reported a protocol providing a greater than 90% chance to obtain a sufficient islet yield for adult pig islet xenotransplantation into no human primates [20].…”

Section: Newborn or Neonatal (Aged 1-5 Days) Islet-like Cell Clustersmentioning

confidence: 99%

“…Additionally, there was a positive relationship between isolated islet number and the number of islets/cm 2 or with the percentage of large islets shown by the pancreas biopsies. Pig pancreases containing more than 82 islets/cm 2 and more than 42% of large islets (>100 μm); thus, enabled more than 120,000 islet equivalents to be harvested in 90% of the cases [20].…”

Section: Etc To the Contrary The Isolation Technique (Dynamic Versumentioning

confidence: 99%

Xenotransplantation for Islets from Clinical Side

Wang¹,

Liang²,

Nie³

et al. 2017

Xenotransplantation - New Insights

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Islet transplantation can eliminate severe hypoglycemia symptoms caused by conventional treatment, and has the advantages of less trauma and complications, which is considered as the most promising treatment for type 1 diabetes mellitus (T1DM). Regulatory guidance is needed for a standard pig source. In section 1, the regulation of medical grade designed pathogen free (DPF) donor pig for clinical xenotransplantation consists of five parts: genetic quality control, microbiological surveillance, formula feeds, specification of pathological diagnosis, and requirements of environment and housing facilities. In section 2, we present the current approach and progress in pig donor selecting, pancreatic digestion, isolation and preparation of porcine islet grafts, identification and quality assessment of final islet product in clinical trials. The liver is currently the most preferred site for islet transplantation, even though it is far from ideal. A large number of alternative sites have been used for islet transplantation in experimental animal models to provide improved engraftment and long-term survival. In Section 3, we introduce some commonly used sites in xenotransplantation. The benefits and drawbacks of each parameter above are discussed in an attempt to decide which is the most suitable for clinical use and to direct future research.

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“…Adult pig is regarded as the primary donor source of islet xenografts, which can supply an adequate amount of viable islet cells and start functioning immediately after implantation (O'Neil et al, 2001;Dufrane et al, 2006). More than 200 000 islet cells with high purity (80%-95%) can be isolated from an adult pig donor (Ricordi et al, 1990;Inoue et al, 1992).…”

Section: Adult and Young Pig Isletsmentioning

confidence: 99%

异种胰岛移植中供体猪的筛选: 现状与进展

Zhu

Lyu

et al. 2014

J. Zhejiang Univ. Sci. B

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Abstract:Islet transplantation is an attractive treatment of type 1 diabetes mellitus. Xenotransplantation, using the pig as a donor, offers the possibility of an unlimited supply of islet grafts. Published studies demonstrated that pig islets could function in diabetic primates for a long time (>6 months). However, pig-islet xenotransplantation must overcome the selection of an optimal pig donor to obtain an adequate supply of islets with high-quality, to reduce xenoantigenicity of islet and prolong xenograft survival, and to translate experimental findings into clinical application. This review discusses the suitable pig donor for islet xenotransplantation in terms of pig age, strain, structure/function of islet, and genetically modified pig.

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Parameters favouring successful adult pig islet isolations for xenotransplantation in pig‐to‐primate models

Abstract: Morphological screening of the pig pancreas before isolation, optimal blood exsanguination, WIT <10 min, and an endotoxin content <30 EU/mg in Liberase PI batches determine successful pig islet isolation for xenotransplantation in primates.

Cited by 67 publications

References 22 publications

Enhanced Prediction of Porcine Islet Yield and Posttransplant Outcome Using a Combination of Quantitative Histomorphometric Parameters and Flow Cytometry

Enhanced Prediction of Porcine Islet Yield and Posttransplant Outcome Using a Combination of Quantitative Histomorphometric Parameters and Flow Cytometry

Xenotransplantation for Islets from Clinical Side

异种胰岛移植中供体猪的筛选: 现状与进展

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