Microparticle-Embedded Stem Cell Spheroid Composite Enables High-Yield, Effective, and Homogeneous Production of Extracellular Vesicles

초록

Extracellular vesicles (EVs), inherently nanoscale vesicles, hold promise for regenerative applications. However, their broader utility is limited by low production efficiency and heterogeneity. Here, we introduce a three-dimensional (3D) stem cell spheroid platform incorporating transforming growth factor-beta 1 (TGF-beta 1)-loaded microparticles to engineer a spatially modulated microenvironment that enhances cellular viability and homogeneity. This engineering system markedly increased EV production efficiency and enhanced compositional consistency compared with conventional spheroids. EVs produced by this system demonstrated strong chondrogenic stimulation mediated by microRNAs in vitro and exhibited regenerative efficacy in a rat osteoarthritis model, validating the performance of the system. Together, these findings present a microparticle-embedded 3D spheroid system that improves both the production efficiency and compositional consistency of EVs, providing a potential strategy for high-yield EV production in regenerative medicine.

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