| Autor: |
Sekhon, Ujjal Didar Singh, Swingle, Kelsey, Girish, Aditya, Luc, Norman, de la Fuente, Maria, Alvikas, Jurgis, Haldeman, Shannon, Hassoune, Adnan, Shah, Kaisal, Kim, Youjoung, Eppell, Steven, Capadona, Jeffrey, Shoffstall, Andrew, Neal, Matthew D., Li, Wei, Nieman, Marvin, Sen Gupta, Anirban |
| Předmět: |
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| Zdroj: |
Science Translational Medicine; 1/26/2022, Vol. 14 Issue 629, p1-11, 11p |
| Abstrakt: |
Treatment of bleeding disorders using transfusion of donor-derived platelets faces logistical challenges due to their limited availability, high risk of contamination, and short (5 to 7 days) shelf life. These challenges could be potentially addressed by designing platelet mimetics that emulate the adhesion, aggregation, and procoagulant functions of platelets. To this end, we created liposome-based platelet-mimicking procoagulant nanoparticles (PPNs) that can expose the phospholipid phosphatidylserine on their surface in response to plasmin. First, we tested PPNs in vitro using human plasma and demonstrated plasmin-triggered exposure of phosphatidylserine and the resultant assembly of coagulation factors on the PPN surface. We also showed that this phosphatidylserine exposed on the PPN surface could restore and enhance thrombin generation and fibrin formation in human plasma depleted of platelets. In human plasma and whole blood in vitro, PPNs improved fibrin stability and clot robustness in a fibrinolytic environment. We then tested PPNs in vivo in a mouse model of thrombocytopenia where treatment with PPNs reduced blood loss in a manner comparable to treatment with syngeneic platelets. Furthermore, in rat and mouse models of traumatic hemorrhage, treatment with PPNs substantially reduced bleeding and improved survival. No sign of systemic or off-target thrombotic risks was observed in the animal studies. These findings demonstrate the potential of PPNs as a platelet surrogate that should be further investigated for the management of bleeding. A cloak and dagger approach to stanch bleeding: Donor-derived platelet transfusion products have limited availability, high risk of contamination, and a short shelf life. These challenges can be potentially addressed by designing platelet-inspired intravenous hemostatic nanoparticles. To this end, Sekhon et al. engineered platelet-mimicking procoagulant nanoparticles (PPNs) that emulate adhesion, aggregation, and procoagulant functions of platelets in an injury-responsive manner. In vitro studies demonstrated that PPNs could restore thrombin and fibrin in platelet-depleted and fibrinolytic settings resulting in improved clot formation. Studies in rodents demonstrated that PPNs provided hemostatic efficacy in animal models of hemorrhage, without the risk of systemic thrombosis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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