TY - JOUR
T1 - Low molecular weight dextran sulfate
T2 - A strong candidate drug to block IBMIR in clinical islet transplantation
AU - Johansson, H.
AU - Goto, M.
AU - Siegbahn, A.
AU - Elgue, G.
AU - Korsgren, O.
AU - Nilsson, B.
PY - 2006/2
Y1 - 2006/2
N2 - 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.
AB - 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.
KW - Dextran sulfate
KW - IBMIR
UR - http://www.scopus.com/inward/record.url?scp=33644904863&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33644904863&partnerID=8YFLogxK
U2 - 10.1111/j.1600-6143.2005.01186.x
DO - 10.1111/j.1600-6143.2005.01186.x
M3 - Article
C2 - 16426314
AN - SCOPUS:33644904863
SN - 1600-6135
VL - 6
SP - 305
EP - 312
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 2
ER -