Advanced Culture Media as a Cornerstone for the Clinical Translation of Exosome Therapeutics

Abstract

The transition from serum-based culture systems to chemically defined media (CDM) represents a pivotal advancement in the development of therapeutic extracellular vesicles (EVs). Traditional use of fetal bovine serum (FBS) introduces substantial variability and risk of contamination, hampering both clinical translation and mechanistic clarity in EV research. While serum-free (SFM), xeno-free (XF), and animal component-free (ACF) formulations offer incremental improvements, only CDM ensures maximal reproducibility, safety, and the capacity for biomanufacturing at scale. Nonetheless, developing one-size-fits-all CDM remains inherently challenging due to the complex, cell-type-specific metabolic requirements and the unmatched molecular richness of serum. Recent progress has been particularly notable in CDM optimized for mesenchymal stem cells and epithelial cells, enabling both higher EV yield and manipulation of EV cargo toward enhanced therapeutic function. Advances in high-throughput screening (HTS), design of experiments (DoE), and artificial intelligence (AI) now enable systematic optimization of multi-component media formulations, marking a paradigm shift from passive support to active regulation of EV composition and bioactivity. CDM is no longer merely a cleaner alternative but a precision-engineering platform central to the production of next-generation EV therapeutics. As biomanufacturing converges with computational design and automation, the ability to tailor EV content through media engineering may redefine standards in regenerative medicine and cell-free therapy.