The rate of fluid shear stress is a potent regulator for the differentiation of mesenchymal stem cells

Abstract

We have previously demonstrated that the rate of fluid shear stress (ΔSS) can manipulate the fate of mesenchymal stem cells (MSCs) to osteogenic or chondrogenic cells. However, whether ΔSS is comparable to other two means of induction medium and substrate stiffness that have been proven to be potent in differentiation control is unknown. In this study, we subjected MSCs to 1–7 days of osteogenic or chondrogenic chemical induction, or 1–4 days of 37 or 86 kPa of substrate stiffness induction, followed by 20 min of Fast ΔSS (0–0′) or Slow ΔSS (0–2′), which is a laminar FSS that linearly increased from 0 to 10 dyn/cm 2 in 0 (Fast) or 2 min (Slow) and maintained at 10 dyn/cm 2 for a total of 20 min. We found that 20 min of ΔSS could compete with 5 days' chemical and 2 days' substrate stiffness inductions. Our study confirmed that ΔSS is a powerful tool to control the differentiation of MSCs, which stressed the possible application in MSCs linage specification.

Extruded Bioreactor Perfusion Culture Supports the Chondrogenic Differentiation of Human Mesenchymal Stem/Stromal Cells in 3D Porous Poly(ɛ‐Caprolactone) Scaffolds

“…[56] While there are studies reporting the positive effect of fluid perfusion in MSC chondrogenic differentiation on tissue engineering scaffolds, [33,64] others have demonstrated detrimental effects such as tissue hypertrophy, reduced GAG production, and lower cell viabilities. [32,34] Nevertheless, two recent studies highlighting the rate of fluid shear stress as an effective regulator of the chondrogenic differentiation of MSC in 2D culture conditions, [73,74] suggest that when using 3D scaffolds systems, different flow rate magnitudes might also result in different outcomes. In the current study, a mild perfusion flow rate of 0.2 mL min -1 was selected to provide uniform linear fluid velocities along the scaffold, resulting in an interesting enhancement of the hBMSC chondrogenic potential and reduced hypertrophy, in comparison to the non-perfused condition.…”

Mechanical Stimulation on Mesenchymal Stem Cells and Surrounding Microenvironments in Bone Regeneration: Regulations and Applications

“…Therefore, the osteogenic differentiation of MSCs induced by mechanical stimulation is also related to the fluid shear stress caused by cyclical hydrostatic pressure (CHP) in vivo. The ability of shear stress to promote osteogenesis of MSCs has been widely recognized, and shear stress can promote MSC osteogenesis in the absence of a chemical induction medium (Yourek et al, 2010;Yue et al, 2019). MSCs mediate fluid shear stress through primary cilia and mechanosensitive ion channels such as TRPV4 and Piezo1 (Hu et al, 2017;Johnson et al, 2018;Li X. et al, 2019).…”

Synergistic effects of fluid shear stress and adhesion morphology on the apoptosis and osteogenesis of mesenchymal stem cells

“…Fluid flow is also a key mechanical signal regulating stem‐cell differentiation 26,27 . Spatiotemporal flow characteristics such as Reynolds number, steady versus pulsatile (including waveform and frequency), magnitude and duration affect MSCs response 28–31 . Luo et al found that the laminar flow with physiological level has a strong inhibitory effect on the apoptosis of MSCs 32 .…”

“…26,27 Spatiotemporal flow characteristics such as Reynolds number, steady versus pulsatile (including waveform and frequency), magnitude and duration affect MSCs response. [28][29][30][31] Luo et al found that the laminar flow with physiological level has a strong inhibitory effect on the apoptosis of MSCs. 32 In addition, oscillating flow upregulated the expression of osteogenic markers in MSCs and increased the proliferation rate.…”