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Early Passage Dependence of Mesenchymal Stem Cell Mechanics Influences Cellular Invasion and Migration

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Abstract

The cellular structures and mechanical properties of human mesenchymal stem cells (hMSCs) vary significantly during culture and with differentiation. Previously, studies to measure mechanics have provided divergent results using different quantitative parameters and mechanical models of deformation. Here, we examine hMSCs prepared for clinical use and subject them to mechanical testing conducive to the relevant deformability associated with clinical injection procedures. Micropipette aspiration of hMSCs shows deformation as a viscoelastic fluid, with little variation from cell to cell within a population. After two passages, hMSCs deform as viscoelastic solids. Further, for clinical applicability during stem cell migration in vivo, we investigated the ability of hMSCs to invade into micropillar arrays of increasing confinement from 12 to 8 μm spacing between adjacent micropillars. We find that hMSC samples with reduced deformability and cells that are more solid-like with passage are more easily able to enter the micropillar arrays. Increased cell fluidity is an advantage for injection procedures and optimization of cell selection based on mechanical properties may enhance efficacy of injected hMSC populations. However, the ability to invade and migrate within tight interstitial spaces appears to be increased with a more solidified cytoskeleton, likely from increased force generation and contractility. Thus, there may be a balance between optimal injection survival and in situ tissue invasion.

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Acknowledgments

We gratefully acknowledge use of microfabrication facilities of S. Anna and help from S. Vuong (Carnegie Mellon, Chemical Engineering). This work is supported by the NSF (NSF-CBET-0954421 and CMMI-1300476 to KND), fellowships from ARCS, Bertucci, and James C. Meade (STS) and National Center for Regenerative Medicine and Cell Therapy Integrated Services (CTIS) Core Facility of the Case Comprehensive Cancer Center (P30 CA43703 to HML). B.L. acknowledges financial supports from the Agence Nationale de la Recherche (Program Nanotechnologies & Nanosystems 2013 ANR 13-NANO-0011), the Human Frontier Science Program (Grant RGP0040/2012), the Institut Universitaire de France and the Mechanobiology Institute (Singapore).

Author contributions

STS designed research, performed research, analyzed data, wrote the paper. WL performed research, analyzed data. EB designed research, performed research, analyzed data. BL contributed analytic tools, wrote the paper. HML contributed analytic tools, contributed biological samples, wrote the paper. KND designed research, analyzed data, wrote the paper.

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Authors and Affiliations

  1. Department of Chemical Engineering, Carnegie Mellon University, 5000 Forbes Ave., Pittsburgh, PA, 15213, USA

    Stephen T. Spagnol, Elizabeth A. Booth & Kris Noel Dahl

  2. Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA

    Wei-Chun Lin & Kris Noel Dahl

  3. Institut Jacques Monod (IJM), CNRS UMR 7592 & Université Paris Diderot, Paris, France

    Benoit Ladoux

  4. Mechanobiology Institute, National University of Singapore, Singapore, Singapore

    Benoit Ladoux

  5. Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA

    Hillard M. Lazarus

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  1. Stephen T. Spagnol
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  2. Wei-Chun Lin
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Correspondence to Kris Noel Dahl.

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Associate Editor Sriram Neelamegham oversaw the review of this article.

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Spagnol, S.T., Lin, WC., Booth, E.A. et al. Early Passage Dependence of Mesenchymal Stem Cell Mechanics Influences Cellular Invasion and Migration. Ann Biomed Eng 44, 2123–2131 (2016). https://doi.org/10.1007/s10439-015-1508-z

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  • DOI: https://doi.org/10.1007/s10439-015-1508-z

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