Islets from brain-dead donors (BDDs) are being used in the treatment of Type 1 diabetes. However, both donor numbers and islet survival are limited. We explored the clinical potential for islets from non-heart-beating donors (NHBDs), who have lower circulating cytokines, by comparing islets from 10 NHBDs against 12 identically-isolated islets from BDDs over the same time period. The quantity and quality of islets from NHBDs was good. NHBD yielded similar to 12.6% more islets than those of BDDs (505 000 +/- 84 230 vs. 400 970 +/- 172 430 islet equivalent number [IEQ]/pancreas, p = 0.01) with comparable viability. ATP and GTP contents were lower (6.026 +/- 3.076 vs. 18.105 +/- 7.8 nM/mg protein, p = 0.01 and 1.52 +/- 0.87 vs. 3.378 +/- 0.83 nM/mg protein, p = 0.04) and correlated negatively to warm ischemia time (R-2 = 0.8022 and R-2 = 0.7996, respectively). Islets from NHBDs took longer to control hyperglycemia in diabetic mice, but were equally able to sustain euglycemia. With a warm ischemia time (WIT) of <= 25 min, islets from NHBDs are at least as competent as islets from BDDs and should be suitable for clinical use.
Human islets derived from donors after cardiac death are fully biofunctional / Zhao M; Muiesan P; Amiel SA; Srinivasan P; Asare-Anane H; Fairbanks L; Persaud S; Jones P; Jones J; Ashraf S; Littlejohn W; Rela M; Heaton N; Huang GC. - In: AMERICAN JOURNAL OF TRANSPLANTATION. - ISSN 1600-6135. - 7:(2007), pp. 2318-2325. [10.1111/j.1600-6143.2007.01937.x]
Human islets derived from donors after cardiac death are fully biofunctional
Muiesan P;
2007
Abstract
Islets from brain-dead donors (BDDs) are being used in the treatment of Type 1 diabetes. However, both donor numbers and islet survival are limited. We explored the clinical potential for islets from non-heart-beating donors (NHBDs), who have lower circulating cytokines, by comparing islets from 10 NHBDs against 12 identically-isolated islets from BDDs over the same time period. The quantity and quality of islets from NHBDs was good. NHBD yielded similar to 12.6% more islets than those of BDDs (505 000 +/- 84 230 vs. 400 970 +/- 172 430 islet equivalent number [IEQ]/pancreas, p = 0.01) with comparable viability. ATP and GTP contents were lower (6.026 +/- 3.076 vs. 18.105 +/- 7.8 nM/mg protein, p = 0.01 and 1.52 +/- 0.87 vs. 3.378 +/- 0.83 nM/mg protein, p = 0.04) and correlated negatively to warm ischemia time (R-2 = 0.8022 and R-2 = 0.7996, respectively). Islets from NHBDs took longer to control hyperglycemia in diabetic mice, but were equally able to sustain euglycemia. With a warm ischemia time (WIT) of <= 25 min, islets from NHBDs are at least as competent as islets from BDDs and should be suitable for clinical use.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.