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Effects of Physical, Chemical, and Biological Stimulus on h-MSC Expansion and Their Functional Characteristics

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Abstract

Human adult mesenchymal stem or stromal cells (h-MSC) therapy has gained considerable attention due to the potential to treat or cure diseases given their immunosuppressive properties and tissue regeneration capabilities. Researchers have explored diverse strategies to promote high h-MSC production without losing functional characteristics or properties. Physical stimulus including stiffness, geometry, and topography, chemical stimulus, like varying the surface chemistry, and biochemical stimuli such as cytokines, hormones, small molecules, and herbal extracts have been studied but have yet to be translated to industrial manufacturing practice. In this review, we describe the role of those stimuli on h-MSC manufacturing, and how these stimuli positively promote h-MSC properties, impacting the cell manufacturing field for cell-based therapies. In addition, we discuss other process considerations such as bioreactor design, good manufacturing practice, and the importance of the cell donor and ethics factors for manufacturing potent h-MSC.

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Acknowledgments

This work was financially supported by the Engineering Research Center for Cell Manufacturing Technologies (CMaT) of the National Science Foundation under Grant No. EEC-1648035, and by the “Programa de Apoyo Institucional Para la Formación en Estudios de Posgrados en Maestrías y Doctorados de La Universidad del Atlántico, Colombia” by providing DCC a scholarship. Supported by PR-INBRE an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant Number P20 GM103475.

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  1. Ralph E. Martin Department of Chemical Engineering, University of Arkansas, 3202 Bell Engineering Center, Fayetteville, AR, 72701, USA

    David A. Castilla-Casadiego & Jorge Almodovar

  2. Department of Chemical Engineering, University of Puerto Rico Mayagüez, Call Box 9000, Mayagüez, PR, 00681-9000, USA

    Ana M. Reyes-Ramos & Maribella Domenech

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  1. David A. Castilla-Casadiego
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Castilla-Casadiego, D.A., Reyes-Ramos, A.M., Domenech, M. et al. Effects of Physical, Chemical, and Biological Stimulus on h-MSC Expansion and Their Functional Characteristics. Ann Biomed Eng 48, 519–535 (2020). https://doi.org/10.1007/s10439-019-02400-3

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