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

Am J Transplant. 2007 Mar;7(3):707-13. doi: 10.1111/j.1600-6143.2006.01655.x. Epub 2007 Jan 4.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Assay*
  • Blood Glucose / analysis
  • Cell Survival
  • DNA / analysis*
  • Diabetes Mellitus / therapy*
  • Humans
  • Islets of Langerhans / chemistry
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / physiology*
  • Islets of Langerhans Transplantation*
  • Mice
  • Mice, Nude
  • Oxygen Consumption*
  • Prognosis
  • Treatment Outcome

Substances

  • Blood Glucose
  • DNA