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Pluripotent-derived Mesenchymal Stem/stromal Cells: an Overview of the Derivation Protocol Efficacies and the Differences Among the Derived Cells

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Abstract

Mesenchymal stem/stromal cells (MSCs) are remarkable tools for regenerative medicine. Therapeutic approaches using these cells can promote increased activity and viability in several cell types through diverse mechanisms such as paracrine and immunomodulatory activities, contributing substantially to tissue regeneration and functional recovery. However, biological samples of human MSCs, usually obtained from adult tissues, often exhibit variable behavior during in vitro culture, especially with respect to cell population heterogeneity, replicative senescence, and consequent loss of functionality. Accordingly, it is necessary to establish standard protocols to generate high-quality, stable cell cultures, for example, by using pluripotent stem cells (PSCs) in derivation protocols of MSC-like cells since PSCs maintain their characteristics consistently during culture. However, the available protocols seem to generate distinct populations of PSC-derivedMSCs (PSC-MSCs) with peculiar attributes, which do not always resemble bona fide primary MSCs. The present review addresses the developmental basis behind some of these derivation protocols, exposing the differences among them and discussing the functional properties of PSC-MSCs, shedding light on elements that may help determine standard characterizations and criteria to evaluate and define these cells.

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Acknowledgements

MATOS, B.M. received a fellowship from Carlos Chagas Institute (ICC/FIOCRUZ-PR). We thank Wagner Nagib from the Communication Advisory (ASCOM/ICC) for helping to refine the illustrations of this review.

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The idea of the article was conceived due to difficulties to reproduce published MSC derivation protocols. Bruno Moisés de Matos and Anny Waloski Robert performed literature research and data analysis. Marco Augusto Stimamiglio wrote the MSC state of the art introduction. Alejandro Correa, Bruno Moisés de Matos and Anny Waloski Robert contributed to writing the topics about derivation protocols. Graphical abstract, Figs. 2 and 3 were idealized by Bruno Moisés de Matos. Figures 1 and 4, as well as Tables 1 and 2 were idealized and formatted by Anny Waloski Robert. The work was critically revised by all authors, especially Marco Augusto Stimamiglio and Alejandro Correa. All authors approved the present manuscript.

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Correspondence to Alejandro Correa.

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de Matos, B.M., Robert, A.W., Stimamiglio, M.A. et al. Pluripotent-derived Mesenchymal Stem/stromal Cells: an Overview of the Derivation Protocol Efficacies and the Differences Among the Derived Cells. Stem Cell Rev and Rep 18, 94–125 (2022). https://doi.org/10.1007/s12015-021-10258-z

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