title: Frequent mechanical stress suppresses proliferation of mesenchymal stem cells from human bone marrow without loss of multipotency.
abstract: Mounting evidence indicated that human mesenchymal stem cells (hMSCs) are responsive not only to biochemical but also to physical cues, such as substrate topography and stiffness. To simulate the dynamic structures of extracellular environments of the marrow in vivo, we designed a novel surrogate substrate for marrow derived hMSCs based on physically cross-linked hydrogels whose elasticity can be adopted dynamically by chemical stimuli. Under frequent mechanical stress, hMSCs grown on our hydrogel substrates maintain the expression of STRO-1 over 20 d, irrespective of the substrate elasticity. On exposure to the corresponding induction media, these cultured hMSCs can undergo adipogenesis and osteogenesis without requiring cell transfer onto other substrates. Moreover, we demonstrated that our surrogate substrate suppresses the proliferation of hMSCs by up to 90% without any loss of multiple lineage potential by changing the substrate elasticity every 2nd days. Such "dynamic in vitro niche" can be used not only for a better understanding of the role of dynamic mechanical stresses on the fate of hMSCs but also for the synchronized differentiation of adult stem cells to a specific lineage.
authors.affiliation: Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Frank
authors.affiliation: Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kaufmann
authors.affiliation: Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wright
authors.affiliation: Department of Medicine V, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Horn
authors.affiliation: Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany.|Department of Chemistry, Saitama University, 338-8570 Saitama, Japan.
authors.forename: Hiroshi Y
authors.initials: HY
authors.lastname: Yoshikawa
authors.affiliation: Department of Medicine V, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Wuchter
authors.affiliation: Department of Chemistry, Dainton Building, University of Sheffield, Brook Hill, Sheffield, South Yorkshire, S3 7HF, United Kingdom.
authors.forename: Jeppe
authors.initials: J
authors.lastname: Madsen
authors.affiliation: Biocompatibles UK Ltd, Chapman House, Farnham Business Park, Weydon Lane, Farnham, Surrey GU9 8 QL, United Kingdom.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
authors.affiliation: Department of Chemistry, Dainton Building, University of Sheffield, Brook Hill, Sheffield, South Yorkshire, S3 7HF, United Kingdom.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Armes
authors.affiliation: Department of Medicine V, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany.|Institute for Integrated Cell-Material Sciences (WPI iCeMS), Kyoto University, 606-8501 Kyoto, Japan.
authors.forename: Motomu
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D002478:Cells, Cultured; D004548:Elasticity; D015870:Gene Expression; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008954:Models, Biological; D010641:Phenotype; D013314:Stress, Mechanical
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers; C525591:STRO-1 antigen, human