Manufacturing USA: Biomanufacturing of Cell Microparticles from Stem Cells As Novel Thrombotic Therapeutic Agents

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Cell and gene therapies can be used to treat a large array of diseases. Therapy is based on using whole cells or viruses to deliver genes or proteins to the patient. Membrane sacs, known as extracellular vesicles (EVs), are a promising new delivery system. They can target specific types of cells for delivery of their cargo, and can carry proteins, fats and ribonucleic acids. This project will develop EV technology based on specialized cells in the bone marrow that generate platelets. Development of this technology could lead to new strategies for solving long-standing problems in Transfusion Medicine by providing a stable and abundant source of platelets. High school and college students from underrepresented groups will engage in research experiences to stimulate their interest in engineering and biomanufacturing careers. The goal of this project is to develop foundational science and engineering for preparing functional extracellular vesicles (EVs) to enable novel cell and gene therapies. EVs are submicron membrane vesicles that carry RNAs, proteins and lipids from their parent cells. Cells use EVs to communicate with other cells, delivering signals through their content, and targeting a rather narrow range of cell types through receptor-recognition mechanisms based on surface proteins. It is now widely accepted that extracellular vesicles are excellent candidates for enabling safe and potent cell and gene therapies. This project will focus on megakaryocytic microparticles (MPs; a type of extracellular vesicles), which target and deliver cargo to hematopoietic stem & progenitor cells (HSPCs). The most important feature of these MPs is that they specifically target HSPCs and program them to generate more megakaryocytes, the precursors of platelets. This project will develop characterization methods and assays for these MPs so that they can be used to develop robust protocols for generating large MP quantities. Finally, the project will also assess the biological efficacy of these MPs as thrombotic agents using a simple murine model.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.