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ИСТИНА ФИЦ ПХФ и МХ РАН |
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Regenerative medicine is a novel multidisciplinary field aiming at the replacement or regeneration of damaged cells, tissue or organs, to restore or establish normal function. Mesenchymal stem/stromal cells (MSC) represent a promising source of multipotent adult stem and progenitor cells for cell therapy and tissue engineering. MSC produce a wide spectrum of bioactive soluble factors and extracellular vesicles (EV) involving in various reparative and regenerative processes in damaged tissues. Considering the various challenges related to the direct therapeutic use of MSC, one should apply conditioned medium (CM), a combination of cell secreted products and EV (membrane particles transporting cytoplasmic and membrane proteins, bioactive lipids, mRNA, miRNA, etc.), which was shown to mediate most of MSC beneficial effects.To date MSC-CM were tested on many disease models with positive results. However, before the clinical application of this promising pharmaceutical, several issues must be addressed, including optimization of bioprocessing protocols, use of clinically compliant ancillary materials and relevant methods for the standardization and quality control of MSC-CM. We suggested the optimized protocol of human adipose-derived MSC-CM production based on the dynamics of key growth factors secreted by cells during long-term conditioning in clinically compliant media. MSC-CM demonstrated specific activity in vitro by stimulating the migration of human fibroblasts and endothelial cells, which are both important for damaged tissue reparation and regeneration. Considering the complexity of MSC-CM, some approaches were used to overcome its limited stability. Further validation of the suggested approach may enhance the efficacy and stability of MSC-CM.