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Endothelial Cell Protection by Dextran Sulfate: A Novel Strategy to Prevent Acute Vascular Rejection in Xenotransplantation
Author(s) -
Laumonier Thomas,
Mohacsi Paul J.,
Matozan Katja M.,
Banz Yara,
Haeberli André,
Korchagina Elena Y.,
Bovin Nicolai V.,
Vanhove Bernard,
Rieben Robert
Publication year - 2004
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 - 10.1046/j.1600-6143.2003.00306.x
Subject(s) - xenotransplantation , complement system , hamster , hemolysis , medicine , endothelial stem cell , in vivo , transplantation , dextran , in vitro , pharmacology , cytotoxicity , endothelium , antibody , microbiology and biotechnology , immunology , biology , biochemistry
We showed recently that low molecular weight dextran sulfate (DXS) acts as an endothelial cell (EC) protectant and prevents human complement‐ and NK cell‐mediated cytotoxicity towards porcine cells in vitro . We therefore hypothesized that DXS, combined with cyclosporine A (CyA), could prevent acute vascular rejection (AVR) in the hamster‐to‐rat cardiac xenotransplantation model. Untreated, CyA‐only, and DXS‐only treated rats rejected their grafts within 4–5 days. Of the hearts grafted into rats receiving DXS in combination with CyA, 28% survived more than 30 days. Deposition of anti‐hamster antibodies and complement was detected in long‐term surviving grafts. Combined with the expression of hemoxygenase 1 (HO‐1) on graft EC, these results indicate that accommodation had occurred. Complement activity was normal in rat sera after DXS injection, and while systemic inhibition of the coagulation cascade was observed 1 h after DXS injection, it was absent after 24 h. Moreover, using a fluorescein‐labeled DXS (DXS‐Fluo) injected 1 day after surgery, we observed a specific binding of DXS‐Fluo to the xenograft endothelium. In conclusion, we show here that DXS + CyA induces long‐term xenograft survival and we provide evidence that DXS might act as a local EC protectant also in vivo .