Abstract
Islet quality assessment methods for predicting diabetes reversal (DR) following transplantation are needed. We investigated two islet parameters, oxygen consumption rate (OCR) and OCR per DNA content, to predict transplantation outcome and explored the impact of islet quality on marginal islet mass for DR. Outcomes in immunosuppressed diabetic mice were evaluated by transplanting mixtures of healthy and purposely damaged rat islets for systematic variation of OCR/DNA over a wide range. The probability of DR increased with increasing transplanted OCR and OCR/DNA. On coordinates of OCR versus OCR/DNA, data fell into regions in which DR occurred in all, some, or none of the animals with a sharp threshold of around 150-nmol/min mg DNA. A model incorporating both parameters predicted transplantation outcome with sensitivity and specificity of 93 and 94, respectively. Marginal mass was not constant, depended on OCR/DNA, and increased from 2,800 to over 100,000 islet equivalents/kg body weight as OCR/DNA decreased. We conclude that measurements of OCR and OCR/DNA are useful for predicting transplantation outcome in this model system, and OCR/DNA can be used to estimate the marginal mass required for reversing diabetes. Because human clinical islet preparations in a previous study had OCR/DNA values in the range of 100-150-nmol/min mg DNA, our findings suggest that substantial improvement in transplantation outcome may accompany increasedOCR/DNAin clinical islet preparations.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 28-34 |
| Number of pages | 7 |
| Journal | Journal of Investigative Surgery |
| Volume | 23 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2010 |
Bibliographical note
Funding Information:Received December 23, 2008; accepted February 18, 2009. This study was supported by grants from the NIH (NCRR ICR U4Z RR 16606, RO1-DK063108) and the JDRF Center for Islet Transplantation at Harvard Medical School. Human islets used to obtain data in Figure 4 were obtained from various Islet Cell Resource centers administered by the Administrative and Bioinformatics Coordinating Center at the City of Hope National Medical Center and supported by NCRR, NIDDK, and JDRF [20]. We thank Stathis Avgoustiniatos for helpful discussions and Anna Pisania and Amy Lewis for help with the figures. Address correspondence to Prof. Clark K. Colton, Department of Chemical Engineering, MIT, Room 66-452, 25 Ames St., Cambridge, MA 02139, USA. E-mail: ckcolton@mit.edu
Keywords
- Marginal graft
- Mouse bioassay
- Oxygen consumption rate
- Predictive assay
- Rat islets
- Transplantation outcome
