Human islet oxygen consumption rate and DNA measurements predict diabetes reversal in nude mice.
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.
Papas
K K
KK
Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN, USA. papas006@umn.edu
Colton
C K
CK
Nelson
R A
RA
Rozak
P R
PR
Avgoustiniatos
E S
ES
Scott
W E
WE
Wildey
G M
GM
Pisania
A
A
Weir
G C
GC
Hering
B J
BJ
D000818:Animals; D001681:Biological Assay; D001786:Blood Glucose / Q000032:analysis; D002470:Cell Survival; D004247:DNA / Q000032:analysis*; D003920:Diabetes Mellitus / Q000628:therapy*; D006801:Humans; D007515:Islets of Langerhans / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008819:Mice, Nude; D010101:Oxygen Consumption; D011379:Prognosis; D016896:Treatment Outcome
D001786:Blood Glucose; D004247:DNA