Advancing Development of Lyophilized Platelet-Derived Extracellular Vesicles (LEVs) as a Hemostatic Agent for Hemorrhagic Shock and Polytrauma
Abstract
Topic Areas: This proposal is submitted to the FY22 the Broad Agency Announcement for the U.S. Army. The topic areas that are relevant to this proposal are: 1) Developing life-saving resuscitation interventions for TBI and polytrauma/complex injury with the LPEVs; 2) Fielding point-of-injury therapeutic interventions to mitigate secondary effects of brain injury, such as neuroinflammation and intracranial hemorrhage, which are all addressable with LPEVs; 3) Research and development into the delivery of care during transport. LPEVs can be utilized during enroute care or prolonged field care of wounded Warfighters to stop bleeding and organ failure; 4) Regenerative medicine involves the use of innovative technologies such as cell-based treatments to restore Service Members who have suffered combat-related injuries. LPEVs are a regenerative treatment that can help improve the secondary consequences of acute injury to the body or brain. Objectives and Rationale Behind Proposed Work: Uncontrolled hemorrhage is the leading cause of preventable death worldwide and polytrauma is the leading cause of death worldwide in all individuals between the ages of 1-46. In this proposal, we will explore how a dried product derived from human platelets (LPEVs) can stop uncontrolled bleeding and protect organs after polytrauma with traumatic brain injury (TBI). LPEVs stands for lyophilized (dried) platelet extracellular vesicles. We will measure the effects of LPEVs on improving outcomes in models of severe trauma including TBI. This proposal will aim to support the development of a product (LPEVs) in in three ways: first, by optimizing the production and drying process with a focus on product development; second, by demonstrating that optimized LPEVs stop blood loss in a model of trauma and hemorrhage; third, by testing the ability of LPEVs to reduce brain swelling, hemorrhage, and inflammation in the brain using a polytrauma model (TBI+torso trauma+ hemorrhage) in mice. Problem to Be Addressed: Platelets are a critical component in stopping bleeding and forming clot formation in bleeding patients. Preventing blood loss and mitigating TBI and polytrauma can save lives. A variety of blood products can help stop bleeding but are not always available especially in battlefield or austere settings. This proposal will develop a dried product from platelets called lyophilized platelet extracellular vesicles (LPEVs) that we and others have shown can stop bleeding and help improve injury to organs in animal models of trauma. The advantage of a dried product is that it has a longer shelf life (approximately 2 years at room temperature) that can be an adjuvant for pre-hospital care and stop bleeding and protect organs when blood products are not readily available. Platelets can only be stored for 5-7 days at room temperature so they are not a great product for remote locations like the battlefield. Clinical Applications/Benefits and Risks: This research will develop a novel product, LPEVs, that can be used to treat patients who are bleeding especially in remote settings where fully supported medical treatment is not available. This can be applicable not only to military personnel deployed in the field but also to individuals injured in major metropolitan areas where transport time can be lengthy or in remote settings which are not close to hospitals. In addition to blood loss from the body, we plan to investigate hemorrhage in the brain which is the major complication of TBI. We believe this product can reduce hemorrhage in the brain and decrease brain swelling, to improve survival and overall outcomes for patients who suffer traumatic brain injury (TBI) and polytrauma. Benefit to Service members, Veterans, and Their Families: The limited shelf life and refrigeration requirement of standard blood products, such as plasma and platelets, makes it difficult to provide plasma on the battlefield for immediate treatment of bleedi
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310489
Entities
People
- Shibani Pati
Organizations
- United States Army
- University of California, San Francisco