Controlled Production of Mesenchymal Stromal Cell-Derived Extracellular Vesicles

This case study outlines the controlled production of mesenchymal stromal cell-derived extracellular vesicles (EVs) in stirred-tank bioreactors. The study addresses the challenge of developing scalable and standardized manufacturing processes for EVs, which are considered a promising alternative to cell-based therapies. It identifies critical process parameters (CPPs) that impact the yield and quality attributes of EVs, contributing to strategies for tighter control over their production. The results indicate that EV yields in stirred-tank bioreactors are higher compared to static culture systems, with increased secretion observed at low glucose concentrations. The study emphasizes the importance of scalability and reproducibility in EV production, integrating online process monitoring strategies to enhance workflow consistency. Additionally, the implementation of Raman spectroscopy as a process analytical technology (PAT) tool allows for continuous monitoring of glucose concentration, identified as a CPP for EV secretion. This approach supports the development of more reproducible workflows and addresses key challenges in large-scale EV production.