(164d) Engineering Human Mesenchymal Bodies for Exosome Secretion in a Novel 3-D Printed Microchannel Bioreactor.

Human Mesenchymal Stem Cells (hMSCs) and their derived products hold great potential in tissue engineering and as therapeutics in a wide range of diseases. While traditionally expanded in 2D on plastic culture dishes, hMSCs possess the ability to aggregate into “spheroids” which are commonly used as a preconditioning technique to enhance their therapeutic potential by upregulating stemness, immunomodulatory capacity, and anti-inflammatory and pro-angiogenic secretome. While there are a number of methods to form hMSC spheroids, few studies have investigated the impact on aggregate properties stemming from dynamic and static aggregation techniques. Furthermore, recent studies have indicated that the main mechanistic mode of hMSC action occurs through their secretome, including extracellular vesicles/exosomes, which contain therapeutically relevant proteins and nucleic acids. In this study, a novel 3D-printed microchannel bioreactor was developed to dynamically form hMSC spheroids under wave motion in order to assess how dynamic microenvironment conditions alter hMSC properties in relation to statically cultured aggregates, in particular the biogenesis of extracellular vesicles/exosomes. Our study found that dynamic aggregation has impacts on hMSC proliferation, morphology, and exosome production. This study advances our knowledge on a commonly used preconditioning technique that could be beneficial in wound healing, neural tissue regeneration, and autoimmune disorders.