CERSI P.I. and Collaborator: Steven M. Jay, PhD UMCP, Fischell Department of Bioengineering
FDA SME and Collaborator: Steven R. Bauer, Ph.D., CBER FDA
Regulatory Science Challenge
Extracellular vesicles (EVs), including exosomes and other subtypes, have emerging commercial potential for use as cell-derived therapeutics which necessitates development of a specific regulatory approach by the FDA. Over 150 clinical trials involving EVs are ongoing as of May 2020 (clinicaltrials.gov), yet there are currently no quality control standards for EV biomanufacturing that would enable validation of a potential commercial product. The goal of this project is to fill this gap as it relates specifically to mesenchymal stromal cell (MSC)-derived EVs, which are heavily cited in the academic literature as useful for a variety of therapeutic applications and are currently under investigation in several clinical trials.
Project Description and Goals
MSC EVs are associated with many different effects, with one of the most therapeutically relevant being anti-inflammatory properties. In this project, we will first assess whether EV anti-inflammatory activity can be predicted based on the appearance of the EV-producing MSCs. This will be done by comparing microscopic analysis of MSCs to performance of EVs in reducing inflammatory secretions of relevant cell types, such as macrophages. Then, we will design scaffolds to maintain MSCs in the form that yields the most anti-inflammatory activity of EVs to attempt to reproducibly mass produce MSC EVs with predictable activity. This would provide proof-of-concept that design interventions could enhance quality control of MSC EVs, addressing the regulatory challenge identified.