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; Haeberli, André and Rieben, Robert

ISSN:

1600-6135

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:12

Last Modified:

04 May 2014 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)

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