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    Cell Surface Functionalization with Heparin-Conjugated Lipid to Suppress Blood Activation

    Year: 2021

    Journal: Adv. Funct. Mater., Volume 31, MAR

    Authors: Asawa, Kenta; Ishihara, Kazuhiko; Ekdahl, Kristina N.; Nilsson, Bo; Teramura, Yuji

    Organizations: Overseas Challenge Program for Young Researchers [201880046]; Bilateral Joint Research Project (Japan-Sweden) of the Japan Society for the Promotion of Science (JSPS); STINT; Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan [26702017, 18H03528, 15KK0230, 18KK0305, 17K20085, 19K22951]; StemTherapy; Swedish Research Council [2018-04199, 2016-2075-5.1, 2016-04519]; Eurostars, Horizon2020; Translational Research program; Strategic PRomotion for practical application of INnovative medical Technology, TR-SPRINT, from the Japan Agency for Medical Research and Development (AMED)

    Keywords: cell surface modifications; glycocalyx; heparin; ischemia reperfusion injury; phospholipids

    Organ transplantation leads to damage of the endothelial glycocalyx of the transplanted organ, and the activated endothelial surface induces thromboinflammation. The result is dysfunction of the transplanted organ, known as ischemia reperfusion injury (IRI). Long-term graft survival strongly depends on the regulation of IRI. Here the aim is to reconstruct the glycocalyx to regulate blood activation during IRI. Heparin-conjugated lipid (fHep-lipid) is synthesized with 0.6, 1.8, 2.7, 4.5, or 8.0 fragmented heparins per lipid to compare their anticoagulation activity. First, liposome and cells are modified with each fHep-lipid and the surface properties are evaluated. Then the hemocompatibility of the modified human mesenchymal stem cells (hMSCs) is examined in a loop model using human blood. The antithrombin-binding capacity and anti-factor Xa activity of the fHep-lipids depend on the number of conjugated heparins, with efficacy increasing with increasing number of heparins. The modified liposomes are highly negatively charged and show strong anti-factor Xa activity. In addition, the cell surfaces of human erythrocytes and hMSCs can be uniformly modified with fHep-lipid. The whole blood studies reveal that fHep-lipid on hMSCs can prevent generation of thrombin-antithrombin complexes, coagulation markers, and platelet aggregation, whereas unmodified hMSCs trigger activation of the platelet and coagulation systems.
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