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Assessment of human islet viability using various mouse models.
O M Sabek1, D W Fraga, O Minoru
1Department of Surgery, University of Tennessee Health Science Center, 956 Court Avenue, Memphis, TN 38103, USA.
Transplantation Proceedings
|November 22, 2005
Summary
This study found that both diabetic and nondiabetic NOD-scid mouse models consistently predict human islet viability. Optimizing streptozotocin dosage reduced mortality and improved diabetes induction in the diabetic model.
Area of Science:
- Endocrinology
- Transplantation Biology
- Animal Models
Background:
- Accurate in vitro viability tests for human islets are lacking, necessitating in vivo animal models for predicting transplant success.
- The diabetic mouse model is a proposed standard for human islet viability assessment, but streptozotocin induction protocols are inconsistent and mortality rates are high.
- NOD-scid mice are commonly used in islet transplantation research.
Purpose of the Study:
- To compare the predictive accuracy of nondiabetic and diabetic NOD-scid mouse models for human islet viability.
- To optimize streptozotocin dosage for improved diabetes induction and reduced mortality in the diabetic model.
- To establish a reliable method for assessing human islet function post-transplantation.
Main Methods:
- Diabetes was induced in NOD-scid mice using varying streptozotocin concentrations (100-200 mg/kg).
- Islet viability was assessed in both diabetic (assessing normoglycemia and C-peptide levels post-transplant) and nondiabetic (measuring C-peptide response to glucose challenge) models.
- 2000 human islet equivalents were transplanted into both groups using identical techniques.
Main Results:
- Titrating streptozotocin dose from 200 to 100 mg/kg significantly decreased mouse mortality from 40% to 10% and increased diabetes induction from 55% to 81%.
- Testing 23 human islet isolations demonstrated complete consistency in viability results between the nondiabetic and diabetic NOD-scid mouse models.
- Both models effectively predicted human islet viability, offering a reliable alternative to current in vitro methods.
Conclusions:
- The nondiabetic NOD-scid mouse model provides a consistent and reliable alternative for predicting human islet viability, comparable to the optimized diabetic model.
- Optimizing streptozotocin induction protocols enhances the utility of the diabetic NOD-scid mouse model.
- These findings support the use of either model for robust human islet viability assessment in research settings.