Response of mesenchymal stem cells to shear stress in tissue-engineered vascular grafts

Abstract

Aim: Recent studies have demonstrated that mesenchymal stem cells (MSCs) can differentiate into endothelial cells. The effect of shear stress on MSC differentiation is incompletely understood, and most studies have been based on two-dimensional systems. We used a model of tissue-engineered vascular grafts (TEVGs) to investigate the effects of shear stress on MSC differentiation. Methods: MSCs were isolated from canine bone marrow. The TEVG was constructed by seeding MSCs onto poly-ε-caprolactone and lactic acid (PCLA) scaffolds and subjecting them to shear stress provided by a pulsatile bioreactor for four days (two days at 1 dyne/cm 2 to 15 dyne/cm 2 and two days at 15 dyne/cm 2 ). Results: Shear stress significantly increased the expression of endothelial cell markers, such as platelet-endothelial cell adhesion molecule-1 (PECAM-1), VE-cadherin, and CD34, at both the mRNA and protein levels as compared with static control cells. Protein levels of alpha-smooth muscle actin (α-SMA) and calponin were substantially reduced in shear stresscultured cells. There was no significant change in the expression of α-SMA, smooth muscle myosin heavy chain (SMMHC) or calponin at the mRNA level. Conclusion: Shear stress upregulated the expression of endothelial cell-related markers and downregulated smooth muscle-related markers in canine MSCs. This study may serve as a basis for further investigation of the effects of shear stress on MSC differentiation in TEVGs.

The role of mechanical stimuli in the vascular differentiation of mesenchymal stem cells

“…Specifically, the first study showed that murine MSCs subjected to a shear stress of 15 dyn/cm 2 express VEGF, but significantly decrease their expression of other growth factors -such as TGF-β1, as well as PDGF and its receptor -which are known to guide stem cells towards the SMC lineage (Wang et al, 2008). Similarly, Dong et al have shown an increase in endothelial markers at both the mRNA and protein levels, whereas SMC markers, such as SMA and calponins, decrease after subjecting canine MSCs to a shear stress of 15 dyn/ cm 2 over 2 days (Dong et al, 2009). Furthermore, the effect of shear stress on differentiation has been shown to vary depending on stress ) shear stress express endothelial markers, including CD31, vWF and VEGFR2.…”

“…For example, bone-marrow-derived MSCs from a number of species are able to differentiate into endothelial-like cells when they are stimulated through physiological shear stress conditions (Engelmayr et al, 2006;Bai et al, 2010;Huang et al, 2010;Maul et al, 2011;Dong et al, 2009;Kim et al, 2011). Likewise, MSCs derived from human adipose tissue (hASCs) (Bassaneze et al, 2010;Zhang et al, 2011;Shojaei et al, 2013) and MSCs from other sources, such as amniotic fluid cells ) and human placenta (Wu et al, 2008), have also been shown to differentiate into endothelial-like cells under shear stress (see Table 1 for a summary).…”

“…Orbital shakers (or rotating disks) rotate the medium-coated disk so that the medium flows concentrically, thus generating laminar or turbulent shear stress over cells that are seeded onto the bottom of the disk (Fischer et al, 2009;Zhang et al, 2009;Bassaneze et al, 2010). Tubular shear stress systems perfuse medium through a tubular scaffold, the inner layer of which is seeded with MSCs Dong et al, 2009;O'Cearbhaill et al, 2008). Microfluidic systems contain submillimeter-sized modules that are made out of gel, such as collagen, and filled with the cells of choice; these modules are then packed into a chamber with pillars to hold them in place, before the chamber is connected to a flow circuit to undergo fluid perfusion (Bruzewicz et al, 2008;Khan and Sefton, 2010;Khan et al, 2012).…”

“…According to two independent studies, it appears that shear stress promotes endothelial differentiation, while downregulating differentiation towards a SMC phenotype (Wang et al, 2008;Dong et al, 2009). Specifically, the first study showed that murine MSCs subjected to a shear stress of 15 dyn/cm 2 express VEGF, but significantly decrease their expression of other growth factors -such as TGF-β1, as well as PDGF and its receptor -which are known to guide stem cells towards the SMC lineage (Wang et al, 2008).…”

Vascular Grafting Strategies in Coronary Intervention

“…Although, Wu et al did not report the presence of ECs or their markers, bone marrow mesenchymal stems cells (MSCs), a small portion of the mononuclear cell fraction, have been successfully differentiated into ECs in vitro (Dong et al, 2009;Moby et al, 2011). The controlled in vitro differentiation of bone marrow MSCs to smooth muscle-like and endothelial-like cells can be achieved through supplement manipulation of the culture media (Zhao et al, 2010).…”