title: The role of current product release criteria for identification of human islet preparations suitable for clinical transplantation.
abstract: BACKGROUND
  Alloimmunity, autoimmunity, and nonspecific inflammation are known to be potential determinants for long-term islet survival and insulin independence. Sufficient islet mass is a key determinant. But islet engraftment and posttransplant survival may also depend on functional characteristics of the graft. This study investigated the significance of current product release criteria for the transplantation outcome.
  
  
  METHODS
  Fourty five consecutive transplanted human islet preparations and their functional outcomes were analyzed. Islet mass was determined according to standard criteria: purity by light microscopy, viability by dye exclusion and Insulin secretory response to static glucose incubation. Islet graft function was monitored for > or = 1 year. Islet function was defined as full (FF), partial (PF), or nonfunction (NF) based on serum C-peptide levels and insulin independence.
  
  
  RESULTS
  All islet grafts displayed primary function. Islet mass [IEQ/kg BW]: 7331.3 +/- 679.7 (FF), 5821.3 +/- 546.7 (PF), 6468.6 +/- 658.5 (NF), (FF vs PF p = .032) Purity [%] 86.9 +/- 3.1 (FF), 76.0 +/- 2.87 (PF), 88.2 +/- 2.3 (NF) (FF vs PF P =.045, PF vs NF, P = 0.01). (4) Viability [%]:89.2 +/- 2 (FF), 86.2 +/- 1.7 (PF), 87.3 +/- 1.8 (NF) (ns). Stimulation index (SI): 20 +/- 6.3 (FF), 80.2 +/- 28.2 (PF), 21.6 +/- 3.5 (NF) (ns) No correlation was observed between SI and any other parameter nor between SI and C-peptide levels. Islet mass significantly correlated with C-peptide levels at 6 and 12 months after transplantation for functioning grafts.
  
  
  CONCLUSIONS
  Stringent product release criteria allow identification of islet preparations suitable for clinical transplantation. However, currently used parameters are not predictive of long-term graft function, indicating that further refined quality assessments including apoptosis and resistance to early inflammation, are required to assess the primary engrafted islet mass.
authors.affiliation: 3rd Medical Department, Center of Internal Medicine, University Hospital, Giessen, Germany. michael.eckhard@innere.med.uni-giessen.de
authors.forename: M
authors.initials: M
authors.lastname: Eckhard
authors.forename: D
authors.initials: D
authors.lastname: Brandhorst
authors.forename: D
authors.initials: D
authors.lastname: Winter
authors.forename: C
authors.initials: C
authors.lastname: Jaeger
authors.forename: H
authors.initials: H
authors.lastname: Jahr
authors.forename: R G
authors.initials: RG
authors.lastname: Bretzel
authors.forename: M D
authors.initials: MD
authors.lastname: Brendel
mesh_terms: D001331:Automation; D002469:Cell Separation / Q000379:methods; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000033:anatomy & histology / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000502:physiology; D020858:Tissue and Organ Harvesting / Q000379:methods*; D017211:Treatment Failure
chemical_list: D007328:Insulin