Improved human pancreatic islet isolation for a prospective cohort study of islet transplantation vs best medical therapy in type 1 diabetes mellitus

Arch Surg. 2005 Aug;140(8):735-44. doi: 10.1001/archsurg.140.8.735.


Hypothesis: A local multiorgan donor pancreas procurement program can provide a source for optimized isolation of purified viable islets for transplantation into patients with type 1 diabetes mellitus receiving best medical therapy.

Design: Prospective before-after cohort study.

Setting: Tertiary referral center.

Patients: Glycemic control was assessed in 10 patients with diabetes-induced renal dysfunction who were enrolled in a best medical therapy program and then crossed over to islet transplantation.

Interventions: Thirty human pancreata were retrieved from local multiorgan donors and consecutively processed with intraductal collagenase perfusion, continuous digestion, and density gradient purification (group 1, n = 9) or similarly processed but impure tissue fractions cultured in vitro and then repurified to retrieve additional islets (group 2, n = 21). Islets were implanted by percutaneous portal embolization, providing more than 10 000 islet equivalents (IE) per kilogram of body weight (infusions from 1-3 donors per patient) under cover of antithymocyte globulin, sirolimus, or mycophenolate mofetil and tacrolimus.

Main outcome measures: Islet yields, purity, and cell viability (caspase 3, terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine 5-triphosphate nick-end labeling stain, and insulin secretion in vitro) were compared. In patients, monitored metabolic parameters were C-peptide secretion, insulin requirements, glycemic excursion, and hemoglobin A(1c) (HbA(1c)).

Results: For group 1 vs group 2, no differences were observed in pancreas age (43 vs 44 years), cold storage (5 vs 4 hours), or weight (73 vs 82 g). Group 2 yielded 453 690 IE vs 214 109 IE in group 1 (P = .002). Grafts contained 50% or more endocrine cells in both groups. No difference occurred in cell viability or insulin secretion. Islets from 90% of group 2 pancreata met release criteria for transplantation. C-peptide secretion was detected in all recipients and persisted with a median follow-up to 12 months (range, 6-21 months) after full islet transplantation. Daily insulin dependence was reversed in all patients for at least 3 months. Five patients resumed small insulin doses. Compared with the best care program, all patients had improved metabolic stability. The mean +/- SE HbA(1c) level at entry into the study was 7.8% +/- 0.5%, and this decreased to 6.9% +/- 0.2% after best care (P = .38) and further to 6.2% +/- 0.2% at 6 months after transplantation (P = .002 vs entry; P = .15 vs best care; analysis of variance).

Conclusions: Local pancreas donor retrieval with islet isolation and culture conditioning enabled an offer of islets for transplantation for 90% of consecutively processed pancreata. Isolated islets secreted insulin during prolonged follow-up after implantation into patients, yielding metabolic control comparable with that achieved by best medical therapy.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Analysis of Variance
  • Blood Glucose / analysis
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / surgery*
  • Female
  • Follow-Up Studies
  • Graft Rejection
  • Graft Survival
  • Humans
  • Insulin / therapeutic use*
  • Islets of Langerhans / cytology*
  • Islets of Langerhans Transplantation / adverse effects
  • Islets of Langerhans Transplantation / methods*
  • Male
  • Middle Aged
  • Monitoring, Physiologic / methods
  • Probability
  • Prospective Studies
  • Risk Assessment
  • Severity of Illness Index
  • Tissue and Organ Harvesting
  • Transplantation Immunology / physiology*
  • Treatment Outcome


  • Blood Glucose
  • Insulin