title: Compaction of islets is detrimental to transplant outcome in mice.
abstract: BACKGROUND
  Despite recent progress in clinical islet transplantation, the cumulative world experience remains small. Optimizing protection of islets throughout the isolation, purification, and peritransplant period remains critical to outcome. We herein investigate the potential detrimental impact of maintaining islets in a pelleted state for periods preceding implantation. We hypothesize that periods of islet compaction lead to impairment if islet function in vivo.
  
  
  METHODS
  In this study, 250-islet marginal mass transplants were conducted in the BALB/c syngeneic mouse model using islets either preincubated as an islet pellet or suspended in culture during the 30 min immediately preceding transplant. Nonfasting blood glucose, intraperitoneal glucose tolerance test, graft histology, and graft insulin content were all used to monitor graft function up to four weeks posttransplant.
  
  
  RESULTS
  Maintaining islets in a compact pellet for 30 min prior to transplantation significantly reduces the proportion of transplant recipients that achieve normoglycemia (from 100% to 38%, P=0.026) and increases the proportion of apoptotic beta-cells.
  
  
  CONCLUSIONS
  Our findings confirm that damage induced by sustained islet compaction results in poor graft outcome in mice. These findings raise concerns relating to potential damage to human islets prior to clinical transplantation, and this will be explored in further studies.
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Alberta, Edmonton AB, Canada.
authors.forename: Shaheed
authors.initials: S
authors.lastname: Merani
authors.forename: Colleen
authors.initials: C
authors.lastname: Schur
authors.forename: Wayne
authors.initials: W
authors.lastname: Truong
authors.forename: Victor K
authors.initials: VK
authors.lastname: Knutzen
authors.forename: Jonathan R T
authors.initials: JR
authors.lastname: Lakey
authors.forename: Colin C
authors.initials: CC
authors.lastname: Anderson
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
authors.forename: A M James
authors.initials: AM
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D006085:Graft Survival; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000737:chemistry / Q000166:cytology / Q000293:injuries*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D020858:Tissue and Organ Harvesting
chemical_list: D007328:Insulin