title: Human islets derived from donors after cardiac death are fully biofunctional.
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 approximately 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 <or=25 min, islets from NHBDs are at least as competent as islets from BDDs and should be suitable for clinical use.
authors.affiliation: Diabetes Research Group, King's College London School of Medicine, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Zhao
authors.forename: P
authors.initials: P
authors.lastname: Muiesan
authors.forename: S A
authors.initials: SA
authors.lastname: Amiel
authors.forename: P
authors.initials: P
authors.lastname: Srinivasan
authors.forename: H
authors.initials: H
authors.lastname: Asare-Anane
authors.forename: L
authors.initials: L
authors.lastname: Fairbanks
authors.forename: S
authors.initials: S
authors.lastname: Persaud
authors.forename: P
authors.initials: P
authors.lastname: Jones
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.forename: S
authors.initials: S
authors.lastname: Ashraf
authors.forename: W
authors.initials: W
authors.lastname: Littlejohn
authors.forename: M
authors.initials: M
authors.lastname: Rela
authors.forename: N
authors.initials: N
authors.lastname: Heaton
authors.forename: G C
authors.initials: GC
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D002470:Cell Survival; D016207:Cytokines / Q000097:blood; D016757:Death, Sudden, Cardiac / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D010179:Pancreas / Q000033:anatomy & histology; D014019:Tissue Donors
chemical_list: D016207:Cytokines