Microgravity-driven Rab27B activation amplifies mesenchymal stem cell-derived extracellular vesicle production and functions

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are emerging as promising treatments for immunomodulation and tissue regeneration. However, the scalable production of functionally enhanced EVs remains a critical challenge. This study introduces microgravity culture using a three-dimensional (3D) rotating cell culture system as a novel strategy to optimize MSC-EVs yield and bioactivity. Methods We first investigated the effects of microgravity on the proliferation and stemness of human umbilical cord-derived MSCs (UCMSCs). The yield of microgravity-derived EVs (µg-EVs) was quantified by nanoparticle tracking analysis. The function of µg-EVs was analyzed by proteomic profiling and further assessed by macrophage polarization and osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Proteomic analysis of UCMSCs was performed to further explore the underlying mechanisms of EVs biogenesis and functional activity under microgravity condition. Results Microgravity culture significantly enhanced UCMSCs proliferation and stemness. Compared with conventional static culture, EVs production increased by 7.7-fold under microgravity. Functionally, µg-EVs more effectively promoted macrophage polarization toward the anti-inflammatory M2 phenotype and significantly enhanced the osteogenic differentiation capacity of PDLSCs. Mechanistically, Rab27B upre

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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