Upscaling Human Mesenchymal Stromal Cell Production In A Novel Vertical-Wheel Bioreactor Enhances Extracellular Vesicle Secretion, Cargo Profile

Human mesenchymal stem cells (hMSCs) are crucial in regenerative medicine due to their potential in tissue repair and treating autoimmune diseases. However, the impact of 3D dynamic bioreactor microenvironments on hMSC-derived extracellular vesicles (EVs) remains poorly understood. This study investigates the effects of shear stress, cell aggregation, and substrate changes on the secretion and cargo profiles of hMSC-EVs in a novel vertical-wheel bioreactor system.
Our findings demonstrate that the bioreactor microenvironment significantly enhances EV secretion by 2.5-fold and upregulates the expression of EV biogenesis markers and glycolysis genes compared to static 2D cultures. The microRNA cargo in EVs from the bioreactor culture was also altered, including the upregulation of miR-10, 19a, 19b, 21, 132, and 377. Proteomics analysis revealed upregulation of metabolic, autophagy, and ROS-related proteins in EVs from the bioreactor compared to 2D cultures.
This study provides valuable insights into the bio-manufacturing of stem cell-derived EVs for cell-free therapy applications, particularly in treating neurological disorders such as ischemic stroke, Alzheimer's disease, and multiple sclerosis.
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