Endothelial cell protection by dextran sulfate: a novel strategy to prevent acute vascular rejection in xenotransplantation

Laumonier, Thomas; Mohacsi, Paul J; Matozan, Katja M; Banz, Yara; Haeberli, André; Korchagina, Elena Y; Bovin, Nicolai V; Vanhove, Bernard; Rieben, Robert (2004). Endothelial cell protection by dextran sulfate: a novel strategy to prevent acute vascular rejection in xenotransplantation. American journal of transplantation, 4(2), pp. 181-7. Oxford: Wiley-Blackwell 10.1046/j.1600-6143.2003.00306.x

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Herz und Gefässe 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Thromboselabor Kinderklinik [discontinued]
UniBE Contributor:	Matozan, Katja, Banz Wälti, Yara Sarah, Häberli, André, Rieben, Robert
ISSN:	1600-6135
Publisher:	Wiley-Blackwell
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:12
Last Modified:	02 Mar 2023 23:23
Publisher DOI:	10.1046/j.1600-6143.2003.00306.x
PubMed ID:	14974938
Web of Science ID:	000188644100006
URI:	https://boris.unibe.ch/id/eprint/31673 (FactScience: 196321)