Extracellular vesicles (EVs) are produced by essentially all types of human cells and are part of the communication network that keeps cells in their optimal state and allows them to respond to changes in their environment. As such, they can be harnessed to transfer therapeutic cargo to cells in the case of disease or injury, and thus represent a promising therapeutic technology for development. This project focused on increasing understanding of EV biology and applying what was learned to improving the biomanufacturing of this emerging class of biotechnology. One objective was to better understand the way in which EVs from mesenchymal stem cells (MSCs) are able to promote certain biological outcomes, such as the growth of new blood vessels. Our work revealed that a specific type of RNA, call long non-coding RNA (lncRNA), plays an important role in this process. We identified particular lncRNAs of interest for therapeutic delivery and demonstrated that EVs loaded with these lncRNAs could indeed improve therapeutic outcomes, specifically in a wound healing model. Another objective was to understand how the condition of cells when they produce EVs affects the EVs themselves. We found that cells respond profoundly to the mechanical stimuli they experience with respect to the amount and activity of the EVs they produce. This knowledge can be used to design devices and systems for future scalable biomanufacturing of therapeutic EVs. A final research objective was to improve quality control of EV production. We made important strides in identifying conditions for production, separation, and storage of EVs that should help normalize EV preparations towards generating a more reproducible and reliable product.

This project also contributed to broader impacts beyond research. A partnership was established with Eleanor Roosevelt High School in Greenbelt, MD allowing students to get hands-on experience in bioengineering research as well as an introduction to college-level engineering facilities and operations. This was accomplished via internships as well as a “BIOE Crash Course” program that brought dozens of students to the University of Maryland campus for hands-on activities. There was also strong integration with community research, education, and diversity programs throughout the project, as students associated with the Women in Engineering program as well as the Louis Stokes Alliance for Minority Participation were able to work on the project and learn more about EVs and biomanufacturing. Finally, training and educational advances were made, as numerous students from the high school, undergraduate, and graduate levels participated in research and received teaching on EVs and biomanufacturing, which was new and additive to their normal curriculum. Overall, the research and educational goals of this project were achieved, with the outcome of moving the field of EV biomanufacturing closer to a clinical reality that could eventually benefit millions of patients and provide biotechnology job opportunities for many in the community.

Last Modified: 06/23/2023
Modified by: Steven M Jay