title: Achievement of insulin independence in three consecutive type-1 diabetic patients via pancreatic islet transplantation using islets isolated at a remote islet isolation center.
abstract: BACKGROUND
  As a result of advances in both immunosuppressive protocols and pancreatic islet isolation techniques, insulin independence has recently been achieved in several patients with type 1 diabetes mellitus via pancreatic islet transplantation (PIT). Although the dissemination of immunosuppressive protocols is quite easy, transferring the knowledge and expertise required to isolate a large number of quality human islets for transplantation is a far greater challenge. Therefore, in an attempt to centralize the critical islet processing needed for islet transplantation and to avoid the development of another islet processing center, we have established a collaborative islet transplant program between two geographically distant transplant centers.
  
  
  METHODS
  Three consecutive patients with type 1 diabetes mellitus with a history of severe hypoglycemia and metabolic instability underwent PIT at the Methodist Hospital (TMH), Houston, Texas, using pancreatic islets. All pancreatic islets were isolated from pancreata procured in Houston and subsequently transported for isolation to the Human Islet Cell Processing Facility of the Diabetes Research Institute (DRI) at the University of Miami, Miami, Florida. Pancreatic islets were isolated at DRI after enzymatic ductal perfusion (Liberase-HI) by the automated method (Ricordi Chamber) using endotoxin-free and xenoprotein-free media. After purification, the islets were immediately transported back to TMH and transplanted via percutaneous transhepatic portal embolization. Immunosuppression consisted of sirolimus, tacrolimus, and daclizumab.
  
  
  RESULTS
  After donor cross-clamp in Houston, donor pancreata arrived at DRI and the isolation process began within 6.5 hr in all cases (median, 5.4 hr; range, 4.8-6.5 hr). At the completion of the isolation process, the islets were immediately transported back to TMH and transplanted. All three patients attained sustained insulin independence after transplantation of 395,567, 394,381, and 563,206 pancreatic islet equivalents (IEQ), respectively. Despite insulin independence, the first two patients received less than 10,000 IEQ/kg; therefore, to increase their functional pancreatic islet reserve, they underwent a second islet transplant with 326,720 and 768,132 IEQ, respectively. Posttransplantation follow-up for these three patients is 4, 3, and 0.5 months, respectively. The mean glycosylated hemoglobin values have been dramatically reduced in the first two patients. In addition, the mean amplitude of glycemic excursions have also been reduced in all three recipients (patient 1: before transplantation 197 mg/dL vs. after transplantation 61 mg/dL; patient 2: before transplantation 202 mg/dL vs. after transplantation 52 mg/dL; patient 3: before transplantation 245 mg/dL vs. after transplantation 58 mg/dL) after PIT. All pancreatic islet allografts demonstrated the ability to respond to an in vitro glucose stimulus at the DRI before shipment and at TMH after shipment and final processing with a median stimulation index of 2.1 and 2.2, respectively. None of the transplant recipients have had a hyper- or hypoglycemic episode since PIT and no complications have occurred.
  
  
  CONCLUSIONS
  These early data demonstrate that (1) pancreatic islets remain viable after shipment to remote transplant sites; (2) pancreatic islet isolation techniques and experience can be concentrated at a small number of regional facilities that could supply islets to remote transplant centers; and (3) insulin independence via PIT can be achieved using a remote pancreatic islet isolation center.
authors.affiliation: Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Goss
authors.forename: Angela P
authors.initials: AP
authors.lastname: Schock
authors.forename: F Charles
authors.initials: FC
authors.lastname: Brunicardi
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Goodpastor
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Garber
authors.forename: George
authors.initials: G
authors.lastname: Soltes
authors.forename: Merle
authors.initials: M
authors.lastname: Barth
authors.forename: Tatiana
authors.initials: T
authors.lastname: Froud
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Alejandro
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D003299:Cooperative Behavior; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D004435:Eating; D005500:Follow-Up Studies; D006085:Graft Survival; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood*; D007373:Interinstitutional Relations; D007515:Islets of Langerhans / Q000502:physiology; D016381:Islets of Langerhans Transplantation; D008875:Middle Aged; D011183:Postoperative Complications; D009927:Tissue and Organ Procurement / Q000458:organization & administration*; D014184:Transplantation, Homologous
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin