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Platelet glycoprotein VI-dependent thrombus stabilization is essential for the intraportal engraftment of pancreatic islets.
Am. J. Transplant., DOI: 10.1111/ajt.16375 (2020)
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
Language
english
Publication Year
2020
HGF-reported in Year
2020
ISSN (print) / ISBN
1600-6135
e-ISSN
1600-6143
Publisher
Wiley
Publishing Place
Hoboken, NJ
Reviewing status
Peer reviewed
Institute(s)
Institute of Pancreatic Islet Research (IPI)
POF-Topic(s)
90000 - German Center for Diabetes Research
Research field(s)
Helmholtz Diabetes Center
PSP Element(s)
G-502600-005
Grants
Deutsche Forschungsgemeinschaft
WOS ID
WOS:000590351100001
Scopus ID
85096798783
PubMed ID
33099857
Erfassungsdatum
2020-12-19