Osteogenic Effects of Rest Inserted and Continuous Cyclic Tensile Strain on hASC Lines with Disparate Osteodifferentiation Capabilities

Abstract

We investigated the effects of two types of cyclic tensile strain, continuous and rest inserted, on osteogenic differentiation of human adipose-derived adult stem cells (hASCs). The influence of these mechanical strains was tested on two hASC lines having different mineral deposition potential, with one cell line depositing approximately nine times as much calcium as the other hASC line after 14 days of culture in osteogenic medium on tissue culture plastic. Results showed that both continuous (10% strain, 1 Hz) and rest inserted cyclic tensile strain (10% strain, 1 Hz, 10 s rest after each cycle) regimens increased the amount and rate of calcium deposition for both high and low calcium depositing hASC lines as compared to unstrained controls. The response was similar for both types of tensile strain for a given cell line, however, cyclic tensile strain had a much stronger osteogenic effect on the high calcium depositing hASC line, suggesting that mechanical loading has a greater effect on cell lines that already have an innate ability to produce bone as compared to cell lines that do not. This is the first study to investigate the osteodifferentiation effects of cyclic tensile strain on hASCs and the first to show that both continuous (10%, 1 Hz) and rest inserted (10%, 1 Hz, 10 s rest) cyclic tensile strain accelerate hASC osteodifferentiation and increase calcium accretion.

2010 Nicolas Andry Award: Multipotent Adult Stem Cells from Adipose Tissue for Musculoskeletal Tissue Engineering

“…In particular, findings suggest that a rounded cell shape (via threedimensional scaffolds or micromass culture) is a critical factor in the induction of the chondrogenic phenotype, and thus physical interactions with the extracellular matrix may have a significant effect on maintaining ASC phenotype over the long term [35]. This evidence suggests that it will be possible to exploit such mechanoinductive stimuli to modulate the chondrogenic differentiation and function of ASCs in conjunction with more traditional biochemical growth factors [38,51,54].…”

Review of biophysical factors affecting osteogenic differentiation of human adult adipose-derived stem cells

“…Table 3 shows an overview of studies using tensile strain stimulus for osteogenic induction of ASCs. One study compared effects of uniaxial, continuous and interrupted strain for 4 h/day for up to 14 days (Hanson et al 2009). Similarly enhanced osteogenesis was observed with both types of strain compared with static culture, judging by measurement of calcium deposition.…”

“…They reported the application of strain significantly reduced age-related increase in adipogenesis in a magnitude-dependent manner, as assessed by formation of oil droplets and expression of the adipogenic marker Bglap1 . Importantly, lack of sensitivity to interruptions of applied strain distinguishes ASCs from BMSCs (Hanson et al 2009); strain modification of age-related increase in adipogenesis has important implications for osteogenesis since these processes may balance each other (Luu et al 2009;Tokuzawa et al 2010). …”

“…Hanson and colleagues observed less variation in mineralization by two cell lines when cells were grown on flexplates necessary for strain application. This effect was attributed to the influence of substrate elasticity (Hanson et al 2009). Inter-individual variation in osteogenic response was observed, but higher cell density and more elastic substrate were noted to reduce this variation.…”

“…Additionally, nanoscale topographical features in growth substrates influence stem cell behavior (Teo et al 2010). Finally, elasticity has a plausible effect on osteogenesis of ASC (Hanson et al 2009;Engler et al 2006;McCullen et al 2010b;Joshi and Webb 2008).…”