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Open AccessArticle

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

1
Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, 27-10, Lomonosovsky av., Moscow 119191, Russia
2
Faculty of Medicine, Lomonosov Moscow State University, 27-1, Lomonosovsky av., Moscow 119192, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(7), 1656; https://doi.org/10.3390/ijms20071656
Received: 20 March 2019 / Revised: 29 March 2019 / Accepted: 30 March 2019 / Published: 3 April 2019
(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine)
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. View Full-Text
Keywords: regenerative medicine; mesenchymal stem/stromal cells; conditioned medium; secretome; growth factors; manufacturing; quality control; regression analysis regenerative medicine; mesenchymal stem/stromal cells; conditioned medium; secretome; growth factors; manufacturing; quality control; regression analysis
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Sagaradze, G.; Grigorieva, O.; Nimiritsky, P.; Basalova, N.; Kalinina, N.; Akopyan, Z.; Efimenko, A. Conditioned Medium from Human Mesenchymal Stromal Cells: Towards the Clinical Translation. Int. J. Mol. Sci. 2019, 20, 1656.

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