Low molecular weight dextran sulfate: A strong candidate drug to block IBMIR in clinical islet transplantation

H. Johansson, Masafumi Goto, A. Siegbahn, G. Elgue, O. Korsgren, B. Nilsson

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

The instant blood-mediated inflammatory reaction (IBMIR) is triggered in clinical islet transplantation when human pancreatic islets come in contact with blood and may explain the initial tissue loss associated with this procedure. Low molecular weight dextran sulfate (LMW-DS; MM 5000), today available for clinical use, inhibits both complement and coagulation activation. In a tubing loop model, LMW-DS at concentrations ranging from 0.01 to 1 g/L showed a dose-dependent inhibition of IBMIR with an inhibition of coagulation and complement activation and less consumption of platelets and other blood cells. In blood or plasma APTT was demonstrated to be an excellent method for monitoring the LMW-DS concentration both in vitro and in vivo in a nonhuman primate model. The toxicity was assessed using a glucose challenge test and the pharmacokinetics was tested in the nonhuman primate model. Here, we present a tentative protocol for using LMW-DS in clinical islet transplantation.

Original languageEnglish
Pages (from-to)305-312
Number of pages8
JournalAmerican Journal of Transplantation
Volume6
Issue number2
DOIs
Publication statusPublished - 2006 Feb 1

Keywords

  • Dextran sulfate
  • IBMIR

ASJC Scopus subject areas

  • Immunology

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