title: Aging enhances the vulnerability of mesenchymal stromal cells to uniaxial tensile strain-induced apoptosis.
abstract: Mechanical priming can be employed in tissue engineering strategies to control the fate and differentiation pattern of mesenchymal stromal cells. This is relevant to regenerative medicine whereby mechanical cues can promote the regeneration of a specific tissue type from mesenchymal precursors. The ability of cells to respond to mechanical forces is dependent upon mechanotransduction pathways that involve membrane-associated proteins, such as integrins. During the aging process changes in the mechanotransduction machinery may influence how cells from aged individuals respond to mechanical priming. In this study mesenchymal stromal cells were prepared from young adult and aged rats and exposed to uniaxial tensile strain at 5% and 10% for 3 days, or 2.5% for 7 days. Application of 5% tensile strain had no impact on cell viability. In contrast, application of 10% tensile strain evoked apoptosis and the strain-induced apoptosis was significantly higher in the mesenchymal stromal cells prepared from the aged rats. In parallel to the age-related difference in cellular responsiveness to strain, an age-related decrease in expression of α2 integrin and actin, and enhanced lipid peroxidation was observed. This study demonstrates that mesenchymal stem cells from aged animals have an altered membrane environment, are more vulnerable to the pro-apoptotic effects of 10% tensile strain and less responsive to the pro-osteogenic effects of 2.5% tensile strain. Thus, it is essential to consider how aged cells respond to mechanical stimuli in order to identify optimal mechanical priming strategies that minimise cell loss, particularly if this approach is to be applied to an aged population.
authors.affiliation: Department of Physiology, School of Medicine, Trinity College Dublin, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Ireland.
authors.forename: Katey
authors.initials: K
authors.lastname: McKayed
authors.affiliation: Trinity Centre for Bioengineering, Trinity College Dublin, Ireland.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Prendergast
authors.affiliation: Department of Physiology, School of Medicine, Trinity College Dublin, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Ireland. Electronic address: vacmpbll@tcd.ie.
authors.forename: Veronica A
authors.initials: VA
authors.lastname: Campbell
mesh_terms: D000199:Actins / Q000378:metabolism; D000375:Aging; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002470:Cell Survival; D039421:Integrin alpha2 / Q000378:metabolism; D015227:Lipid Peroxidation; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D044968:Regenerative Medicine / Q000379:methods; D013314:Stress, Mechanical; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D000199:Actins; D039421:Integrin alpha2; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Aging; Apoptosis; Mesenchymal stromal cells; Tensile strain