Compaction of islets is detrimental to transplant outcome in mice

Shaheed Merani, Colleen Schur, Wayne Truong, Victor K. Knutzen, Jonathan R T Lakey, Colin C. Anderson, Camillo Ricordi, A. M James Shapiro

Research output: Contribution to journalArticle

9 Citations (Scopus)

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. CONCLUSION. 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.

Original languageEnglish
Pages (from-to)1472-1476
Number of pages5
JournalTransplantation
Volume82
Issue number11
DOIs
StatePublished - Dec 1 2006

Fingerprint

Transplants
Transplantation
Islets of Langerhans Transplantation
Glucose Tolerance Test
Blood Glucose
Histology
Insulin

Keywords

  • Glucose homeostasis
  • Islet injury
  • Islet transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Merani, S., Schur, C., Truong, W., Knutzen, V. K., Lakey, J. R. T., Anderson, C. C., ... Shapiro, A. M. J. (2006). Compaction of islets is detrimental to transplant outcome in mice. Transplantation, 82(11), 1472-1476. https://doi.org/10.1097/01.tp.0000243166.64244.3d

Compaction of islets is detrimental to transplant outcome in mice. / Merani, Shaheed; Schur, Colleen; Truong, Wayne; Knutzen, Victor K.; Lakey, Jonathan R T; Anderson, Colin C.; Ricordi, Camillo; Shapiro, A. M James.

In: Transplantation, Vol. 82, No. 11, 01.12.2006, p. 1472-1476.

Research output: Contribution to journalArticle

Merani, S, Schur, C, Truong, W, Knutzen, VK, Lakey, JRT, Anderson, CC, Ricordi, C & Shapiro, AMJ 2006, 'Compaction of islets is detrimental to transplant outcome in mice', Transplantation, vol. 82, no. 11, pp. 1472-1476. https://doi.org/10.1097/01.tp.0000243166.64244.3d
Merani S, Schur C, Truong W, Knutzen VK, Lakey JRT, Anderson CC et al. Compaction of islets is detrimental to transplant outcome in mice. Transplantation. 2006 Dec 1;82(11):1472-1476. https://doi.org/10.1097/01.tp.0000243166.64244.3d
Merani, Shaheed ; Schur, Colleen ; Truong, Wayne ; Knutzen, Victor K. ; Lakey, Jonathan R T ; Anderson, Colin C. ; Ricordi, Camillo ; Shapiro, A. M James. / Compaction of islets is detrimental to transplant outcome in mice. In: Transplantation. 2006 ; Vol. 82, No. 11. pp. 1472-1476.
@article{b822554a348c47e6901b5b42ff2ef0ac,
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. CONCLUSION. 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.",
keywords = "Glucose homeostasis, Islet injury, Islet transplantation",
author = "Shaheed Merani and Colleen Schur and Wayne Truong and Knutzen, {Victor K.} and Lakey, {Jonathan R T} and Anderson, {Colin C.} and Camillo Ricordi and Shapiro, {A. M James}",
year = "2006",
month = "12",
day = "1",
doi = "10.1097/01.tp.0000243166.64244.3d",
language = "English",
volume = "82",
pages = "1472--1476",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Compaction of islets is detrimental to transplant outcome in mice

AU - Merani, Shaheed

AU - Schur, Colleen

AU - Truong, Wayne

AU - Knutzen, Victor K.

AU - Lakey, Jonathan R T

AU - Anderson, Colin C.

AU - Ricordi, Camillo

AU - Shapiro, A. M James

PY - 2006/12/1

Y1 - 2006/12/1

N2 - 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. CONCLUSION. 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.

AB - 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. CONCLUSION. 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.

KW - Glucose homeostasis

KW - Islet injury

KW - Islet transplantation

UR - http://www.scopus.com/inward/record.url?scp=33845718541&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845718541&partnerID=8YFLogxK

U2 - 10.1097/01.tp.0000243166.64244.3d

DO - 10.1097/01.tp.0000243166.64244.3d

M3 - Article

C2 - 17164719

AN - SCOPUS:33845718541

VL - 82

SP - 1472

EP - 1476

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 11

ER -