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Chen, C. ; Rawat, D.* ; Samikannu, B.* ; Bender, M.* ; Preissner, K.T.* ; Linn, T.*

Platelet glycoprotein VI-dependent thrombus stabilization is essential for the intraportal engraftment of pancreatic islets.

Am. J. Transplant., DOI: 10.1111/ajt.16375 (2020)
Publ. Version/Full Text Research data DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Platelet activation and thrombus formation have been implicated to be detrimental for intraportal pancreatic islet transplants. The platelet-specific collagen receptor glycoprotein VI (GPVI) plays a key role in thrombosis through cellular activation and the subsequent release of secondary mediators. In aggregometry and in a microfluidic dynamic assay system modeling flow in the portal vein, pancreatic islets promoted platelet aggregation and triggered thrombus formation, respectively. While platelet GPVI deficiency did not affect the initiation of these events, it was found to destabilize platelet aggregates and thrombi in this process. Interestingly, while no major difference was detected in early thrombus formation after intraportal islet transplantation, genetic GPVI deficiency or acute anti-GPVI treatment led to an inferior graft survival and function in both syngeneic mouse islet transplantation and xenogeneic human islet transplantation models. These results demonstrate that platelet GPVI signaling is indispensable in stable thrombus formation induced by pancreatic islets. GPVI deficiency resulted in thrombus destabilization and inferior islet engraftment indicating that thrombus formation is necessary for a successful intraportal islet transplantation in which platelets are active modulators.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Basic (laboratory) Research / Science ; Coagulation And Hemostasis ; Graft Survival ; Islet Transplantation ; Molecular Biology; Type-1 Diabetes-mellitus; Tissue Factor; In-vivo; Basement-membrane; Activation; Collagen; Gpvi; Transplantation; Blood; Mechanisms
ISSN (print) / ISBN 1600-6135
e-ISSN 1600-6143
Publisher Wiley
Publishing Place Hoboken, NJ
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)
Grants Deutsche Forschungsgemeinschaft