Compaction of islets is detrimental to transplant outcome in mice.
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.
Merani
Shaheed
S
Department of Surgery, Faculty of Medicine, University of Alberta, Edmonton AB, Canada.
Schur
Colleen
C
Truong
Wayne
W
Knutzen
Victor K
VK
Lakey
Jonathan R T
JR
Anderson
Colin C
CC
Ricordi
Camillo
C
Shapiro
A M James
AM
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
D007328:Insulin