Human islet oxygen consumption rate and DNA measurements predict diabetes reversal in nude mice

K. K. Papas, C. K. Colton, R. A. Nelson, P. R. Rozak, E. S. Avgoustiniatos, W. E. Scott, G. M. Wildey, A. Pisania, G. C. Weir, B. J. Hering

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

There is a need for simple, quantitative and prospective assays for islet quality assessment that are predictive of islet transplantation outcome. The current state-of-the-art athymic nude mouse bioassay is costly, technically challenging and retrospective. In this study, we report on the ability of 2 parameters characterizing human islet quality: (1) oxygen consumption rate (OCR), a measure of viable volume; and (2) OCR/DNA, a measure of fractional viability, to predict diabetes reversal in nude mice. Results demonstrate that the probability for diabetes reversal increases as the graft's OCR/DNA and total OCR increase. For a given transplanted OCR dose, diabetes reversal is strongly dependent on OCR/DNA. The OCR and OCR/DNA (the 'OCR test') data exhibit 89% sensitivity and 77% specificity in predicting diabetes reversal in nude mice (n = 86). We conclude that the prospective OCR test can effectively replace the retrospective athymic nude mouse bioassay in assessing human islet quality prior to islet transplantation.

Original languageEnglish (US)
Pages (from-to)707-713
Number of pages7
JournalAmerican Journal of Transplantation
Volume7
Issue number3
DOIs
StatePublished - Mar 2007
Externally publishedYes

Keywords

  • Islet potency
  • Nude mice
  • Oxygen consumption rate
  • Quality assessment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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