Introduction. Cardiovascular diseases represent the leading cause of mortality in Western countries.1 Vascular endothelial injury may lead to the development of atherosclerosis. An immediate restoration of vascular endothelial lining is critical for the prevention of atherosclerotic vascular diseases.2,3 However, current solutions fail to achieve the desired reendothelization. Previous studies injected mesenchymal stem cells (MSCs) into a vascular injury site in hope of restoring damaged vascular endothelial layers. Subjected to shear stress exerted by blood flow, MSCs differentiated into correct cell types needed for repair, but in some instances, MSCs gave a rise to ectopic tissue formation.4 This uncontrolled differentiation hinders the use of MSCs for the repair of vascular endothelial injury. Thus, researchers aim to discover how fluid shear stress impacts the mechanotransduction of MSCs and ultimately contributes to the differentiation process.4,5 Good understanding will allow us to control the differentiation of stem cells into cells of corresponding tissues for repair. Methods. MSCs were harvested from bone marrows of mice’s femurs.6 Microfluidic study was utilized to mimic physiological environments in blood vessels.4 MSCs were seeded onto channels, and serum-supplemented medium flowed through the channel onto the seeded MSCs. The consequent morphological changes of MSCs were analyzed using confocal fluorescence microscopy. HUTS-4 staining and anti-integrin β-1 antibodies were used to study mechanosensing.5 Fluorescence-activated cell sorter analysis and gene-knockout were utilized to study mechanotransuduction pathway. Results. Shear stress of 1.3 Pa induced the rearrangement of cytoskeleton parallel to the direction of fluid flow. On the contrary, MSCs under static conditions or under shear stress below 0.2 Pa showed no morphological changes.4 Studies show that shear stress activated integrin β-1 and the activation of integrin β-1 induced the cytoskeletal rearrangement.5 The cytoskeletal rearrangement was associated with the expression of endothelial expression markers such as Von Willebrand Factor (vWF) and CD31.7 Furthermore, RAS/ERK1/2-depedent signal pathway was linked to the cytoskeletal rearrangement and was essential for the endothelial differentiation.5,8 Conclusions. Studies have found that mechanotransduction modulates the differentiation of MSCs and that MSCs, preconditioned with shear stress, has enhanced reendothelialization capacity in vivo.5,7 Furthermore, shear stress-treated MSCs were less prone to intimal hyperplasia and thrombosis.5 In summary, better understanding of how mechanotransduction modulates the differentiation of stem cells will allow us to control the differentiation of stem cells as needed in treating cardiovascular diseases.
- Tresoldi C, Pellegata AF, Mantero S. Cells and stimuli in small-caliber blood vessel tissue engineering. Regen Med. 2015;10(4):505-27.
- Bergheanu SC, Bodde MC, Jukema JW. Pathophysiology and treatment of atherosclerosis : Current view and future perspective on lipoprotein modification treatment. Neth Heart J. 2017;25(4):231-242.
- Spence JD. Recent advances in pathogenesis, assessment, and treatment of atherosclerosis. F1000Res. 2016;5
- Zheng W, Xie Y, Zhang W, et al. Fluid flow stress induced contraction and re-spread of mesenchymal stem cells: a microfluidic study. Integr Biol (Camb). 2012;4(9):1102-11.
- Cheng M, Guan X, Li H, et al. Shear stress regulates late EPC differentiation via mechanosensitive molecule-mediated cytoskeletal rearrangement. PLoS ONE. 2013;8(7):e67675.
- Dan P, Velot É, Decot V, Menu P. The role of mechanical stimuli in the vascular differentiation of mesenchymal stem cells. J Cell Sci. 2015;128(14):2415-22.
- Cui X, Zhang X, Guan X, et al. Shear stress augments the endothelial cell differentiation marker expression in late EPCs by upregulating integrins. Biochem Biophys Res Commun. 2012;425(2):419-25.
- Obi S, Masuda H, Shizuno T, et al. Fluid shear stress induces differentiation of circulating phenotype endothelial progenitor cells. Am J Physiol, Cell Physiol. 2012;303(6):C595-606.