Therapies that use a patient's own cells show great promise in the treatment of a variety of diseases, including cancer. Manufacturing therapeutic cells reliably is a major challenge. This project will define design and control parameters to make this possible. The initial focus is on producing a cell-based therapy for wound healing. If successful, the technology that is developed could lead to breakthroughs in treatments for other life-threatening diseases. An education plan will promote opportunities and training at the high school through post-graduate levels. A progressive program at the high school level that impacts hundreds of students per year will increase exposure to research opportunities and promote retention in STEM career paths. Community outreach programs will also be supported, and research findings will be integrated to enhance these programs.
Establishing new criteria for rational design of biomanufacturing approaches for therapeutic mesenchymal stem/stromal cell (MSC) exosomes is the focus of this project. Exosomes have therapeutic bioactivity, including vascularization. Many of the therapeutic effects associated with cell-based therapies are now being ascribed to protein, nucleic acid, and/or lipid transfer from exosomes and other extracellular vesicles secreted by implanted cells. The general hypothesis is that MSC exosome production and therapeutic bioactivity are defined by the cell culture microenvironment and the status of producer MSCs. The research objectives are to: 1) investigate the mechanism of vascularization bioactivity; 2) investigate the mechanism of cell density effects on production; and 3) develop quantitative predictive criteria to enable quality control of exosome production. If successful, this technology will impact patients by enabling new therapeutic options for wound repair, and ischemic and other diseases.
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.
