Islet oxygen consumption rate dose predicts insulin independence for first clinical islet allotransplants

J. P. Kitzmann, D. O'Gorman, T. Kin, Angelika C Gruessner, P. Senior, S. Imes, Rainer W G Gruessner, A. M J Shapiro, Klearchos K Papas

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background. Human islet allotransplantation for the treatment of type 1 diabetes is in phase III clinical trials in the U.S. and is the standard of care in several other countries. Current islet product release criteria include viability based on cell membrane integrity stains, glucose-stimulated insulin release, and islet equivalent (IE) dose based on counts. However, only a fraction of patients transplanted with islets that meet or exceed these release criteria become insulin independent following 1 transplant. Measurements of islet oxygen consumption rate (OCR) have been reported as highly predictive of transplant outcome in many models. Method. In this article we report on the assessment of clinical islet allograft preparations using OCR dose (or viable IE dose) and current product release assays in a series of 13 first transplant recipients. The predictive capability of each assay was examined and successful graft function was defined as 100% insulin independence within 45 days post-transplant. Results. OCR dose was most predictive of CTO. IE dose was also highly predictive, while glucoses stimulated insulin release and membrane integrity stains were not. Conclusion. OCR dose can predict CTO with high specificity and sensitivity and is a useful tool for evaluating islet preparations prior to clinical human islet allotransplantation.

Original languageEnglish (US)
Pages (from-to)1985-1988
Number of pages4
JournalTransplantation Proceedings
Volume46
Issue number6
DOIs
StatePublished - 2014

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Oxygen Consumption
Insulin
Transplants
Coloring Agents
Glucose
Phase III Clinical Trials
Standard of Care
Type 1 Diabetes Mellitus
Allografts
Cell Membrane
Sensitivity and Specificity
Membranes
Therapeutics

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Islet oxygen consumption rate dose predicts insulin independence for first clinical islet allotransplants. / Kitzmann, J. P.; O'Gorman, D.; Kin, T.; Gruessner, Angelika C; Senior, P.; Imes, S.; Gruessner, Rainer W G; Shapiro, A. M J; Papas, Klearchos K.

In: Transplantation Proceedings, Vol. 46, No. 6, 2014, p. 1985-1988.

Research output: Contribution to journalArticle

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AU - Imes, S.

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AU - Shapiro, A. M J

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AB - Background. Human islet allotransplantation for the treatment of type 1 diabetes is in phase III clinical trials in the U.S. and is the standard of care in several other countries. Current islet product release criteria include viability based on cell membrane integrity stains, glucose-stimulated insulin release, and islet equivalent (IE) dose based on counts. However, only a fraction of patients transplanted with islets that meet or exceed these release criteria become insulin independent following 1 transplant. Measurements of islet oxygen consumption rate (OCR) have been reported as highly predictive of transplant outcome in many models. Method. In this article we report on the assessment of clinical islet allograft preparations using OCR dose (or viable IE dose) and current product release assays in a series of 13 first transplant recipients. The predictive capability of each assay was examined and successful graft function was defined as 100% insulin independence within 45 days post-transplant. Results. OCR dose was most predictive of CTO. IE dose was also highly predictive, while glucoses stimulated insulin release and membrane integrity stains were not. Conclusion. OCR dose can predict CTO with high specificity and sensitivity and is a useful tool for evaluating islet preparations prior to clinical human islet allotransplantation.

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