N-Acetylcysteine derivative inhibits procoagulant activity of human islet cells.
OBJECTIVE
The early loss of beta cells after islet cell transplantation has been attributed in part to blood coagulation at the implant site. Tissue factor expressed by beta cells and contaminating duct cells is considered to activate this process. Here, we investigated the ability of N-acetyl-L-cysteine to suppress the in vitro procoagulant activity of duct cells and human islet cell preparations.


METHODS
The effects of Nacystelyn, a salt derivative of N-acetyl-L-cysteine, were first assessed on procoagulant activity induced in human plasma by recombinant tissue factor, human primary duct cells or human islet cell preparations. The influence of Nacystelyn on clot formation, platelet counts and D-dimers were measured in a whole blood tubing loop model. Human beta cell viability and insulin synthesis after Nacystelyn treatment were assessed to exclude cytotoxicity of Nacystelyn.


RESULTS
Nacystelyn efficiently inhibited the procoagulant activity of human recombinant tissue factor, primary duct cells and human islet cell preparations at clinically relevant concentrations without cellular toxicity.


CONCLUSIONS
Nacystelyn is a pharmaceutical candidate to reduce early beta cell loss related to tissue factor-dependent coagulation after islet transplantation.
Beuneu
C
C
Institute for Medical Immunology, Université Libre de Bruxelles, rue Adrienne Bolland 8, B-6041, Charleroi, Belgium.
Vosters
O
O
Ling
Z
Z
Pipeleers
D
D
Pradier
O
O
Goldman
M
M
Verhasselt
V
V
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D013925:Thromboplastin / Q000187:drug effects / Q000502:physiology; D014019:Tissue Donors
D013925:Thromboplastin; D000111:Acetylcysteine