Conditioned Medium from Human Mesenchymal Stromal Cells: Towards the Clinical Translation

• Published in: International journal of molecular sciences 2019-04, Vol.20 (7), p.1656
• Main Authors: Sagaradze, Georgy, Grigorieva, Olga, Nimiritsky, Peter, Basalova, Nataliya, Kalinina, Natalia, Akopyan, Zhanna, Efimenko, Anastasia
• Format: Article
• Language: English
• Subjects: Biological activity; Cell adhesion & migration; Cell growth; Chemical compounds; Clinical trials; conditioned medium; Endothelial cells; Fibroblast growth factor 2; Fibroblasts; Growth factors; Hepatocyte growth factor; Manufacturing; mesenchymal stem/stromal cells; Mesenchyme; Pharmacology; Quality control; regenerative medicine; Regression analysis; Secretome; Stromal cells; Tissue engineering; Vascular endothelial growth factor
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20071656

Mesenchymal stem/stromal cells (MSC) remain a promising tool for regenerative medicine as the efficacy of MSC-based cell therapy has been demonstrated for a broad spectrum of indications. Their therapeutic potency is mainly associated with their ability to secrete multiple factors critical for tissue regeneration. Due to comparable effects along with superior safety MSC conditioned medium (MSC-CM) containing a complex of MSC-secreted products is considered a reasonable alternative to cell therapy. However, the lack of standards regulating bioprocessing, use of proper auxiliary materials, and quality control complicates the development of MSC secretome-based therapeutics. In this study, we suggested several approaches addressing these issues. We manufactured 36 MSC-CM samples based on different xeno-free serum-free chemically defined media (DMEM-LG or MSC NutriStem XF) using original protocols and considered total concentrations of regeneration-associated paracrine factors secreted by human adipose-derived MSC at each time-point of conditioning. Using regression analysis, we retrospectively predicted associations between concentrations of several components of MSC-CM and its biological activity to stimulate human dermal fibroblast and endothelial cell migration in vitro as routine examples of potency assays for cell-based products. We also demonstrated that the cell culture medium might affect MSC-CM biological activity to varying degrees depending on the potency assay type. Furthermore, we showed that regression analysis might help to overcome donor variability. The suggested approaches might be successfully applied for other cell types if their secretome was shown to be promising for application in regenerative medicine.