Mechanical conditioning of mesenchymal stem cells (MSCs) has been adopted widely as a biophysical signal to aid tissue engineering applications. The replication of in vivo mechanical signaling has been used in in vitro environments to regulate cell differentiation, and extracellular matrix synthesis, so that both the chemical and mechanical properties of the tissue-engineered construct are compatible with the implant site. While research in these areas contributes to tissue engineering, the effects of mechanical strain on MSC apoptosis remain poorly defined. To evaluate the effects of uniaxial cyclic tensile strain on MSC apoptosis and to investigate mechanotransduction associated with strain-mediated cell death, MSCs seeded on a 2D silicone membrane were stimulated by a range of strain magnitudes for . Mechanotransduction was investigated using the stretch-activated cation channel blocker gadolinium chloride, the -type voltage-activated calcium channel blocker nicardipine, the c-jun -terminal kinase (JNK) blocker D-JNK inhibitor 1, and the calpain inhibitor MDL 28170. Apoptosis was assessed through DNA fragmentation using the terminal deoxynucleotidyl transferase mediated-UTP-end nick labeling method. Results demonstrated that tensile strains of 7.5% or greater induce apoptosis in MSCs. -type voltage-activated calcium channels coupled mechanical stress to activation of calpain and JNK, which lead to apoptosis through DNA fragmentation. The definition of the in vitro boundary conditions for tensile strain and MSCs along with a proposed mechanism for apoptosis induced by mechanical events positively contributes to the development of MSC biology, bioreactor design for tissue engineering, and development of computational methods for mechanobiology.
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December 2008
Research Papers
Mechanisms of Strain-Mediated Mesenchymal Stem Cell Apoptosis
E. M. Kearney,
E. M. Kearney
Trinity Centre for Bioengineering, School of Engineering,
Trinity College Dublin
, Dublin 2, Ireland
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P. J. Prendergast,
P. J. Prendergast
Trinity Centre for Bioengineering, School of Engineering,
Trinity College Dublin
, Dublin 2, Ireland
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V. A. Campbell
V. A. Campbell
Trinity Centre for Bioengineering, School of Engineering,
e-mail: vacmpbll@tcd.ie
Trinity College Dublin
, Dublin 2, Ireland; Department of Physiology, Trinity College Dublin
, Dublin 2, Ireland
Search for other works by this author on:
E. M. Kearney
Trinity Centre for Bioengineering, School of Engineering,
Trinity College Dublin
, Dublin 2, Ireland
P. J. Prendergast
Trinity Centre for Bioengineering, School of Engineering,
Trinity College Dublin
, Dublin 2, Ireland
V. A. Campbell
Trinity Centre for Bioengineering, School of Engineering,
Trinity College Dublin
, Dublin 2, Ireland; Department of Physiology, Trinity College Dublin
, Dublin 2, Irelande-mail: vacmpbll@tcd.ie
J Biomech Eng. Dec 2008, 130(6): 061004 (7 pages)
Published Online: October 9, 2008
Article history
Received:
September 18, 2007
Revised:
May 14, 2008
Published:
October 9, 2008
Citation
Kearney, E. M., Prendergast, P. J., and Campbell, V. A. (October 9, 2008). "Mechanisms of Strain-Mediated Mesenchymal Stem Cell Apoptosis." ASME. J Biomech Eng. December 2008; 130(6): 061004. https://doi.org/10.1115/1.2979870
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