Packaging of supplemented urokinase into alpha granules of in vitro-grown megakaryocytes for targeted nascent clot lysis.

ABSTRACT:

Abstract

Fibrinolytics delivered into the general circulation lack selectivity for nascent thrombi, reducing efficacy and increasing the risk of bleeding. Urokinase-type plasminogen activator (uPA) transgenically expressed within murine platelets provided targeted thromboprophylaxis without causing bleeding but is not clinically feasible. Recent advances in generating megakaryocytes prompted us to develop a potentially clinically relevant means to produce "antithrombotic" platelets from CD34+ hematopoietic stem cell-derived in vitro-grown megakaryocytes. CD34+ megakaryocytes internalize and store in alpha granules (α-granules) single-chain uPA (scuPA) and a plasmin-resistant thrombin-activatable variant (uPAT). Both uPAs colocalized with internalized factor V (FV), fibrinogen and p

SUBMITTER: Poncz M 

PROVIDER: S-EPMC11298819 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature