On-demand production of human platelets in an automated microfluidic bioreactor
Abstract
Objectives: The goal of this project is to develop a scalable and renewable source of human platelets for use in staunching major bleeding after traumatic injury. Normally, platelets are generated in the bone marrow by precursor stem cells. Platelet transfusions require human platelet donations, but demand for platelets far exceeds supply, especially during emergencies such as those resulting in mass casualties. Platelet BioGenesis has developed a process and bioreactor to produce functional human platelets from frozen stocks of established pluripotent non-embryonic stem cell lines within 1-2 days of demand, without requiring human donors. Platelet BioGenesis has established proof of principle by sourcing clinical-grade, human-induced pluripotent stem cells and showing that they can be cultured into functional human platelets that are comparable to donor platelets using a small prototype bioreactor that reproduces the native environment of the bone marrow. This project will industrialize the production process and expand production capacity to increase yield and reduce cost in preparation for clinical testing and use. Objective 1 is to optimize the cell production process. The milestones are to select the best production stem cell line and to improve the cell culture protocol to increase platelet yield, reduce production cost, and meet regulatory requirements. Objective 2 is to expand and optimize the bioreactor device to increase total platelet yield and reduce the overall cost of the bioreactor manufacturing process. The bioreactors will be increased from their current business card size to the size of a tablet computer and will be stacked together to increase output. The key milestone is to increase platelet bioreactor size to produce the equivalent of a single platelet transfusion unit (300 billion platelets) in a stack of ~10 tablet-sized bioreactors within 24-48 hours. Achieving these milestones will enable future human clinical trials to test safety and effectiveness. Safe, sterile, culture-derived human platelets could reach the market by 2023. Problem to be Solved: This project addresses the critical need for new methods to provide life-saving platelet transfusions to wounded Warfighters and civilians, especially during emergencies resulting in mass casualties. It responds to a call from the Combat Casualty Care Research Program of the US Army Medical Research and Materiel Command for new technologies to stop blood loss and limit the deleterious consequences of major bleeding. Improved platelet supply also is sought by the Allergy and Infectious Diseases Radiation Countermeasures Program as a response to a potential radiation accident or attack. This project will develop a new method to provide life-saving platelets for military and civilian use. Platelets are blood cells that promote clot formation at sites of active bleeding. Platelet transfusions stop uncontrolled bleeding and dramatically increase survival after traumatic injury or massive transfusions. They also save lives after severe accidental or deliberate radiation exposure, which damages the body’s ability to produce blood cells. Today, platelets are collected from human volunteer donors. However, because they have a very short shelf life of 5 days and are subject to contamination, the demand greatly exceeds the supply, especially in military theaters or during emergencies with mass casualties. Bioreactor-derived platelets should be sterile, safe for all recipients, and free of contamination. Applicability and Impact: If successful, this project will have a significant impact on clinical medicine by ensuring the availability of platelets that are safe, cost-effective, and available on demand from a renewable source without needing volunteer donors. Platelets are required in all medical facilities that treat victims of trauma and massive radiation exposure, both military and civilian, both in the Unites States and abroad.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810187
Entities
People
- Jonathan Thon
Organizations
- Platelet BioGenesis (United States)
- United States Army