Short communicationAging enhances the vulnerability of mesenchymal stromal cells to uniaxial tensile strain-induced apoptosis
Introduction
Mesenchymal stromal cells can be expanded in culture and mechanically primed towards specific lineages (Sonnaert et al., 2014). These cells are mechano-responsive and the application of mechanical stimuli has been demonstrated to control their differentiation (Kearney et al., 2010; Haugh et al., 2011).
Integrins are mechanosensitive proteins that activate downstream signalling to evoke a response to biophysical stimuli (Popov et al., 2011, Seong et al., 2013). In mesenchymal stem cells the α2 integrins anchor the cells to collagen I (Warstat et al., 2010) and regulate the osteogenic pathway (Kuo et al., 2012; Becerra-Bayona et al., 2012).
We have previously described how the application of cyclic uniaxial tensile strain can regulate the differentiation and viability of young adult rat mesenchymal stromal cells (Kearney et al., 2008, 2010; McMahon et al., 2008). With an increasingly aged population (Lutz et al., 2008) it is pertinent to examine how aged cells respond to biophysical stimuli. The aim of the current study was therefore to examine the effect of aging on the influence of tensile strain on the viability of aged mesenchymal stromal cells.
Section snippets
Culture of mesenchymal stromal cells
Mesenchymal stromal sells were prepared from 3-month old (250–300 g) and 22-month old (700–750 g) Wistar rats (Charles River (UK)), as previously described (Dominici et al., 2006). Animals were sacrificed by CO2 asphyxiation and cervical dislocation in accordance with European guidelines (86/609/EEC). The epiphyses of the femur and tibia were cut and the marrow was flushed out with Dulbecco’s modified Eagle’s medium supplemented with 10% foetal bovine serum (Gibco BRL, Dublin), 100 U/ml
Expression of α2 integrin in rat MSCs is decreased with age
A significant age-related reduction in expression of the α2 subunit of integrin was observed (Fig. 1(a)); (p<0.001, Student’s t-test, n=5). Distribution of α2 integrin in the plasma membrane was localised in dense regions around the membrane indicative of focal adhesion complex formations. Western immunoblot detected α2 integrin expression bands at 165 kDa and a significant 25% decrease in the expression of α2 integrin was observed in MSCs isolated from aged rats (p<0.05, Student’s t-test, n=4).
Expression of actin in MSCs is decreased with age
Discussion
The results of this study demonstrate an age-related reduction in the expression of α2 integrin and actin, in parallel with an age-related increase in lipid peroxidation. The data also demonstrate that MSCs from aged rats are more vulnerable to an induction of apoptosis following exposure to 10% strain. The lower tensile strain of 2.5% is able to evoke osteogenesis (Kearney et al., 2010) and this strain-mediated enhancement of osteogenesis is more pronounced in MSC isolated from young, compared
Conflicts of interest statement
None.
Acknowledgements
This work was funded by Science Foundation Ireland (08/RFP/ENM1361). KMcK was a recipient of a Trinity College Award.
References (18)
- et al.
Influence of select extracellular matrix proteins on mesenchymal stem cell osteogenic commitment in three-dimensional contexts
Acta Biomater.
(2012) - et al.
Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement
Cytotherapy
(2006) - et al.
Regulation of the fate of human mesenchymal stem cells by mechanical and stereo-topographical cues provided by silicon nanowires
Biomaterials
(2012) - et al.
A comparison of the involvement of p38, ERK1/2 and PI3K in growth factor-induced chondrogenic differentiation of mesenchymal stem cells
Biochem. Biophys. Res. Commun.
(2008) - et al.
Integrins, adhesion and apoptosis
Trends Cell Biol.
(1997) - et al.
Are sensory TRP channels biological alarms for lipid peroxidation?
Int. J. Mol. Sci.
(2014) - et al.
Temporal and spatial changes in cartilage-matrix-specific gene expression in mesenchymal stem cells in response to dynamic compression
Tissue Eng. Part A
(2011) - et al.
Overexpression of integrin a2 promotes osteogenic differentiation of hBMSCs from senile osteoporosis through the ERK pathway
Int. J. Clin. Exp. Pathol.
(2013) - et al.
Tensile strain as a regulator of mesenchymal stem cell osteogenesis
Ann. Biomed. Eng.
(2010)
Cited by (2)
Effect of mechanical strain on the pluripotency of murine embryonic stem cells seeded in a collagen-I scaffold
2018, Journal of Orthopaedic Research