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Low Molecular Weight Dextran Sulfate: A Strong Candidate Drug to Block IBMIR in Clinical Islet Transplantation
Author(s) -
Johansson H.,
Goto M.,
Siegbahn A.,
Elgue G.,
Korsgren O.,
Nilsson B.
Publication year - 2006
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2005.01186.x
Subject(s) - islet , transplantation , medicine , in vivo , complement system , pharmacology , pharmacokinetics , coagulation , dextran , immunology , endocrinology , diabetes mellitus , chemistry , biochemistry , biology , immune system , microbiology and biotechnology
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.