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Human Mesenchymal Stem Cells Form Multicellular Structures in Response to Applied Cyclic Strain

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Abstract

Mesenchymal stem cells (MSCs) are a component of many cardiovascular cell-based regenerative medicine therapies. There is little understanding, however, of the response of MSCs to mechanical cues present in cardiovascular tissues. The objectives of these studies were to identify a model system to study the effect of well-defined applied cyclic strain on MSCs and to use this system to determine the effect of cyclic equibiaxial strain on the cellular and cytoskeletal organization of MSCs. When exposed to 10%, 1 Hz cyclic equibiaxial strain for 48 h, MSCs remained viable, retained characteristic gene and protein markers, and rearranged to form multicellular structures defined as clusters and knobs. This novel observation of cluster (overlapping cells surrounded by radial cellular projections) and knob (more dome-like structure containing significantly more cells than a cluster) formation did not involve changes in cytoskeletal proteins and resulted from cellular rearrangements initiated within 8 h of applied strain. Observed cellular responses were found to be dependent on substrate coating, but not on cell density for the 8-fold ranges tested. This system can thus be used to study the mechanoresponse over hours to days of MSCs exposed to applied cyclic strain in the context of cell–cell and cell–matrix interactions.

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Acknowledgments

The authors thank the Georgia Tech/Emory Center for the Engineering of Living Tissues (National Science Foundation Engineering Research Center: NSF EEC-9731643; AMD, RMN, TA), the Ruth L. Kirschstein National Research Service Award (1F32HL076978-01A1; TA), the NIH Cellular and Tissue Engineering Training Program (5T32GM008433-14 and 5T32GM008433-15; AMD), and the Georgia Institute of Technology President’s Fellowship (AMD) for financial support. This material is based upon work supported under a National Science Foundation Graduate Research Fellowship (AMD). Thanks to Garry Duffy for protocols related to the differentiation of MSCs. There are no conflicts of interest for the authors to disclose.

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  1. Parker H. Petit Institute for Biomedical Engineering and Biosciences, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA, 30332-0363, USA

    Adele M. Doyle, Robert M. Nerem & Tabassum Ahsan

  2. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University School of Medicine, 313 Ferst Drive, Suite 2127, Atlanta, GA, 30332-0535, USA

    Adele M. Doyle & Robert M. Nerem

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Doyle, A.M., Nerem, R.M. & Ahsan, T. Human Mesenchymal Stem Cells Form Multicellular Structures in Response to Applied Cyclic Strain. Ann Biomed Eng 37, 783–793 (2009). https://doi.org/10.1007/s10439-009-9644-y

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