Prediction of marginal mass required for successful islet transplantation.
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.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Klearchos K
KK
Papas
Clark K
CK
Colton
Andi
A
Qipo
Haiyan
H
Wu
Rebecca A
RA
Nelson
Bernhard J
BJ
Hering
Gordon C
GC
Weir
Maria
M
Koulmanda
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002452:Cell Count; D004247:DNA / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D005260:Female; D006085:Graft Survival; D007165:Immunosuppression Therapy; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size; D010101:Oxygen Consumption; D011379:Prognosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous
D001786:Blood Glucose; D004247:DNA