title: Early Passage Dependence of Mesenchymal Stem Cell Mechanics Influences Cellular Invasion and Migration.
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.
authors.affiliation: Department of Chemical Engineering, Carnegie Mellon University, 5000 Forbes Ave., Pittsburgh, PA, 15213, USA.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Spagnol
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Lin
authors.affiliation: Department of Chemical Engineering, Carnegie Mellon University, 5000 Forbes Ave., Pittsburgh, PA, 15213, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Booth
authors.affiliation: Institut Jacques Monod (IJM), CNRS UMR 7592 & Université Paris Diderot, Paris, France.|Mechanobiology Institute, National University of Singapore, Singapore, Singapore.
authors.forename: Benoit
authors.initials: B
authors.lastname: Ladoux
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.affiliation: Department of Chemical Engineering, Carnegie Mellon University, 5000 Forbes Ave., Pittsburgh, PA, 15213, USA. krisdahl@cmu.edu.|Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. krisdahl@cmu.edu.
authors.forename: Kris Noel
authors.initials: KN
authors.lastname: Dahl
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods*; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*
keywords: Cell mechanics; Human mesenchymal stem cells; Mechanobiology; Micropipette aspiration