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Islet surface heparinization prevents the instant blood-mediated inflammatory reaction in islet transplantation

Cabric, Sanja; Sanchez, Javier; Lundgren, Torbjorn; Foss, Aksel; Felldin, Marie; Källén, Ragnar LU ; Salmela, Kaija; Tibell, Annika; Tufveson, Gunnar and Larsson, Rolf, et al. (2007) In Diabetes 56(8). p.2008-2015
Abstract
Objective-In clinical islet transplantation, the instant blood-mediated inflammatory reaction (IBMIR) is a major factor contributing to the poor initial engraftment of the islets. This reaction is triggered by tissue factor and monocyte chemoattractant protein (MCP)-1, expressed by the transplanted pancreatic islets when the islets come in contact with blood in the portal vein. All currently identified systemic inhibitors of the IBMIR are associated with a significantly increased risk of bleeding or other side effects. To avoid systemic treatment, the aim of the present study was to render the islet graft blood biocompatible by applying a continuous heparin coating to the islet surface. Research design and methods-A biotin/avidin technique... (More)
Objective-In clinical islet transplantation, the instant blood-mediated inflammatory reaction (IBMIR) is a major factor contributing to the poor initial engraftment of the islets. This reaction is triggered by tissue factor and monocyte chemoattractant protein (MCP)-1, expressed by the transplanted pancreatic islets when the islets come in contact with blood in the portal vein. All currently identified systemic inhibitors of the IBMIR are associated with a significantly increased risk of bleeding or other side effects. To avoid systemic treatment, the aim of the present study was to render the islet graft blood biocompatible by applying a continuous heparin coating to the islet surface. Research design and methods-A biotin/avidin technique was used to conjugate preformed heparin complexes to the surface of pancreatic islets. This endothelial-like coating was achieved by conjugating barely 40 IU heparin per full-size clinical islet transplant. Results-Both in an in vitro loop model and in an allogeneic porcine model of clinical islet transplantation, this heparin coating provided protection against the IBMIR. Culturing heparinized islets for 24 h did not affect insulin release after glucose challenge, and heparin-coated islets cured diabetic mice in a manner similar to untreated islets. Conclusions-This novel pretreatment procedure prevents intraportal thrombosis and efficiently inhibits the IBMIR without increasing the bleeding risk and, unlike other pretreatment procedures (e.g., gene therapy), without inducing acute or chronic toxicity in the islets. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
56
issue
8
pages
2008 - 2015
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000248473100007
  • scopus:34547610974
ISSN
1939-327X
DOI
10.2337/db07-0358
language
English
LU publication?
yes
id
9cd803ea-010a-4725-b72b-651009772df3 (old id 686702)
date added to LUP
2007-12-11 09:59:39
date last changed
2017-10-01 04:37:30
@article{9cd803ea-010a-4725-b72b-651009772df3,
  abstract     = {Objective-In clinical islet transplantation, the instant blood-mediated inflammatory reaction (IBMIR) is a major factor contributing to the poor initial engraftment of the islets. This reaction is triggered by tissue factor and monocyte chemoattractant protein (MCP)-1, expressed by the transplanted pancreatic islets when the islets come in contact with blood in the portal vein. All currently identified systemic inhibitors of the IBMIR are associated with a significantly increased risk of bleeding or other side effects. To avoid systemic treatment, the aim of the present study was to render the islet graft blood biocompatible by applying a continuous heparin coating to the islet surface. Research design and methods-A biotin/avidin technique was used to conjugate preformed heparin complexes to the surface of pancreatic islets. This endothelial-like coating was achieved by conjugating barely 40 IU heparin per full-size clinical islet transplant. Results-Both in an in vitro loop model and in an allogeneic porcine model of clinical islet transplantation, this heparin coating provided protection against the IBMIR. Culturing heparinized islets for 24 h did not affect insulin release after glucose challenge, and heparin-coated islets cured diabetic mice in a manner similar to untreated islets. Conclusions-This novel pretreatment procedure prevents intraportal thrombosis and efficiently inhibits the IBMIR without increasing the bleeding risk and, unlike other pretreatment procedures (e.g., gene therapy), without inducing acute or chronic toxicity in the islets.},
  author       = {Cabric, Sanja and Sanchez, Javier and Lundgren, Torbjorn and Foss, Aksel and Felldin, Marie and Källén, Ragnar and Salmela, Kaija and Tibell, Annika and Tufveson, Gunnar and Larsson, Rolf and Korsgren, Olle and Nilsson, Bo},
  issn         = {1939-327X},
  language     = {eng},
  number       = {8},
  pages        = {2008--2015},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Islet surface heparinization prevents the instant blood-mediated inflammatory reaction in islet transplantation},
  url          = {http://dx.doi.org/10.2337/db07-0358},
  volume       = {56},
  year         = {2007},
}