Engineering Platelets to Increase Coagulability and Effectiveness of Platelet Transfusions in Resuscitation in Bleeding Patients

Project Description Narrative:

Hemorrhage following trauma is a leading cause of death in all socio-economic and geographical backgrounds. There are currently more than 200 firearm-related deaths in Wisconsin each year, with an additional 700-plus non-fatal shootings that can lead to severe disability. These events contribute to dramatic health inequities.

Platelet transfusion is an integral part of balanced resuscitation in hemorrhage management. However, transfused platelets are often ineffective during severe, intractable hemorrhage. There are currently only two major approaches being taken to increase the coagulability of platelets, each of which has drawbacks. A favorable alternative to all these approaches is to develop tools for modifying units of platelets from blood donors (donor platelets) ex vivo, while they are concentrated and stored, prior to transfusion.

This project will test whether engineering protein expression in transfusable platelets can be achieved using state-of-the-art mRNA transfection and delivery systems. Platelets provide a highly optimized way to deliver biomolecules safely and locally to a wound, as they preferentially localize and release their content at wound sites when activated.