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Manufacturing of primed mesenchymal stromal cells for therapy

Abstract

Mesenchymal stromal cells (MSCs) for basic research and clinical applications are manufactured and developed as unique cell products by many different manufacturers and laboratories, often under different conditions. The lack of standardization of MSC identity has limited consensus around which MSC properties are relevant for specific outcomes. In this Review, we examine how the choice of media, cell source, culture environment and storage affects the phenotype and clinical utility of MSC-based products, and discuss the techniques better suited to prime MSCs with specific phenotypes of interest and the need for the continued development of standardized assays that provide quality assurance for clinical-grade MSCs. Bioequivalence between cell products and batches must be investigated rather than assumed, so that the diversity of phenotypes between differing MSC products can be accounted for to identify products with the highest therapeutic potential and to preserve their safety in clinical treatments.

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Fig. 1: The techniques available for the large-scale expansion of MSCs in vitro may lead to diverse changes in cell stemness, heterogeneity and senescence.
Fig. 2: Morphology of MSCs in culture.
Fig. 3: Potential mechanisms of MSC-primed therapeutics.

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Acknowledgements

This work was supported by grants from the National Key Scientific Program (2017CB964902) to J.Q.Y. and J.Z.

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J.Q.Y., J.Z. and J.A. conceived of and wrote the manuscript. J.Q.Y. and J.Z. generated the figures.

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Correspondence to James Q. Yin or James A. Ankrum.

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J.Q.Y. was involved in the production of the rejuvenating MSCM media, marketed by Geno Biotechnology Co. in China. J.A. and J.Z. declare no competing interests.

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Yin, J.Q., Zhu, J. & Ankrum, J.A. Manufacturing of primed mesenchymal stromal cells for therapy. Nat Biomed Eng 3, 90–104 (2019). https://doi.org/10.1038/s41551-018-0325-8

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