Annals of Biomedical Engineering

, Volume 37, Issue 4, pp 783–793

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

  • Adele M. Doyle
  • Robert M. Nerem
  • Tabassum Ahsan
Article

DOI: 10.1007/s10439-009-9644-y

Cite this article as:
Doyle, A.M., Nerem, R.M. & Ahsan, T. Ann Biomed Eng (2009) 37: 783. doi:10.1007/s10439-009-9644-y

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.

Keywords

Regenerative medicineMechanical forcesCyclic strainMechanotransductionCytoskeletonCell–cell contactCell–matrix interaction

Supplementary material

10439_2009_9644_MOESM2_ESM.tif (13 mb)
(TIF 13358 kb)

Copyright information

© Biomedical Engineering Society 2009

Authors and Affiliations

  • Adele M. Doyle
    • 1
    • 2
  • Robert M. Nerem
    • 1
    • 2
  • Tabassum Ahsan
    • 1
  1. 1.Parker H. Petit Institute for Biomedical Engineering and Biosciences, Georgia Institute of TechnologyAtlantaUSA
  2. 2.Wallace H. Coulter Department of Biomedical EngineeringGeorgia Institute of Technology/Emory University School of MedicineAtlantaUSA