Effects of shear stress on differentiation of stem cells into endothelial cells

Table 2 Studies on shear stress regulating endothelial progenitor cell to endothelial differentiation

Cell source	Condition of shear stress	Markers expressed	Function tested	Signaling molecule	Ref.
Human umbilical cord blood derived- EPCs	Rotating-disk-type flow-loading device Shear stress applied ranged from 1 × 10-6 to 5 × 10-5 N/cm2 1, 2 d	VEGFR1, VEGFR2, VE-cadherin, Tie2, VCAM1, integrin αv/β3, E-selectin, eNOS, matrix metalloproteinase 9, and VEGF	-	PI3K/Akt/mTOR	Obi et al[32], 2012
Human cord blood derived-EPCs	Perfusion system. Unidirectional shear stress (0.3 ± 0.1, 6 ± 3 × 10-5 N/cm2) and bidirectional shear stress (0.3 ± 3 × 10-5 N/cm2) 24 h	Tissue factor	-	-	Mazzolai et al[33], 2011
Human peripheral blood mononuclear cells-derived EPCs	Rotating disk-type flow loading device 0.1 to 2.5 × 10-5 N/cm2 24 h	Flk-1, Flt-1 and VE-cadherin	Matrigel tube formation assay	-	Yamamoto et al[34], 2003
Human blood mononuclear cells-derived EPCs	Parallel-plate coculture flow chamber 5 × 10-5 N/cm2 24 h	CD31 and vWF	-	Akt	Ye et al[35], 2008
Human CD34+ hematopoietic progenitor cells	Cone-and-plate apparatus 1.5 × 10-4 N/cm2 24 h	VEGFR2, eNOS, and a VEGFR2 promoter-driven reporter gene	-	HoxA9	Rössig et al[36], 2005
Human peripheral blood mononuclear cells-derived EPCs	Parallel plate flow chamber channel 5 × 10-5, 1.5 × 10-4 and 2.5 × 10-4 N/cm2 for 24 h or 1.5 × 10-4 N/cm2 for 5, 10 and 20 h	Phosphorylated Tie2, phosphorylated Akt andeNOS	reendothelialization assay in nude mouse model	Tie2 /PI3K/Akt	Yang et al[37], 2012
EPCs isolated from rat bone marrow	Flow chamber system 2 × 10-5, 6 × 10-5, 1.2 × 10-4, and 2 × 10-4 N/cm2 12, 24 h	CD31 and vWF	-	Integrins	Cui et al[38], 2012
Human umbilical cord blood derived- EPCs	Parallel plate flow chamber system 1.5 × 10-4 N/cm2 6, 12, and 24 h	VEGFR2, VE-cadherin, vWF, and CD31	Matrigel tube formation assay	miR-34a/Foxj2	Cheng et al[39], 2014
Human peripheral blood mononuclear cells-derived EPCs	Rotating-disk-type flow-loading device. Shear stress applied ranged from 0.1 to 5 × 10-5 N/cm2 6, 12, 24 h	EphrinB2, Notch1/3, Hey1/2, and activin receptor-like kinase 1	-	Sp1	Obi et al[41], 2009
Human peripheral blood mononuclear cells-derived EPCs	Parallel plate-type device 1.5 × 10-4 N/cm2 1 d	CD31, vWF, and ephrinB2	-	p38 and MAPK pathways	Suzuki et al[42], 2012

Akt: Protein kinase B; ALK1: Activin receptor-like kinase 1; Ac-H3: H3 acetylation; eNOS: Endothelial nitric-oxide synthase; BH4: Tetrahydrobiopterin; EPCs: Endothelial progenitor cells; Flk-1: Fetal liver kinase-1; Flt-1: Fms-like tyrosine kinase-1; Foxj2: Forkhead box j2; GTPCH: Guanosine triphosphate cyclohydrolase; KLF2: Krüppel-like factor 2; MAPK: Mitogen-activated protein kinase; miR-34a: MicroRNA-34a; PI3K: Phosphoinositide 3-kinase; PTEN: Tumor suppressor phosphatase and tensin homolog; Tie2: Tyrosine kinase with immunoglobulin and epidermal growth factor homology domain-2; VCAM1: Vascular cell adhesion molecule-1; VE-cadherin: Vascular endothelial-cadherin; VEGFR1: Vascular endothelial growth factor receptor 1; VEGFR2: Vascular endothelial growth factor receptor 2; vWF: Von Willebrand factor .