Objective-Recent studies have illustrated that mesenchymal stem cells possess the potential to differentiate along an endothelial lineage, but the effect of shear on mesenchymal differentiation is unknown. Thus, we developed an in vitro shear stress system to examine the relationship between shear stress and the endothelial differentiation of a murine embryonic mesenchymal progenitor cell line, C3H/10T1/2. Methods and Results-The parallel plate system of fluid shear stress was used. Shear stress significantly induced expression of mature endothelial cell-specific markers in CH3H/10T1/2 cells such as CD31, von Willebrand factor, and vascular endothelial-cadherin at both the mRNA and protein levels with real-time polymerase chain reaction and immunofluorescence analyses, respectively. In addition, shear-induced augmentation of functional markers of the mature endothelial phenotype such as uptake of acetylated low-density lipoproteins and formation of capillary-like structures on Matrigel. Furthermore, shear stress significantly upregulated angiogenic growth factors while downregulating growth factors associated with smooth muscle cell differentiation. T he blood vessel wall is inherently subjected to and affected by the pulsatile hemodynamic stimulus of blood flow within the vascular lumen, and biomechanical forces intrinsically present as a result of this hemodynamic flow are believed to play an important role in vascular development, remodeling, and lesion formation. In particular, cells lining the vascular lumen are constantly subjected to shear stress, a frictional force at the apical endothelial surface exerted by blood flow. 1,2 Shear stress has been recognized as an important modulator of endothelial phenotype, morphology, gene expression, and, especially, differentiation. 3,4 See page 1761 Conclusions-ThisThe ability to influence or control endothelial cell differentiation would have implications for vasculogenesis (neovascularization), understanding the pathogenic physiology behind atherosclerotic lesion formation, use in vascular healing or repair, and use in tissue engineering applications; thus, recent studies have demonstrated the utility of shear stress in provoking endothelial progenitor cell (EPC) differentiation. 4,5 However, these studies have generally used a fairly heterogeneous starting precursor population. Furthermore, the overall small number of EPCs in circulation and the need for ex vivo expansion before use suggests that the EPC may not be the best progenitor for functional application. 6 Recent studies have illustrated that mesenchymal stem cells (MSCs) also possess the potential to differentiate along an endothelial lineage. 7,8 For example, Oswald et al demonstrated endothelial differentiation when MSCs were cultivated in 2% FCS and 50 ng/mL vascular endothelial growth factor (VEGF). 7 Additionally, other studies have revealed the contribution of MSCs to the formation of new vessels and improvements in cardiac function. 9,10 Thus, MSCs may hold the potential to differentiate along end...
Interrupted enoxaparin therapy and age 50 years or older are associated with DVT formation among trauma and general surgery patients. Missed doses occur commonly and are the only identified risk factor for DVT that can be ameliorated by physicians. Efforts to minimize interrupted enoxaparin prophylaxis in patients at risk for DVT should be optimized.
The pulsatile nature of blood flow is a key stimulus for the modulation of vascular cell differentiation. Within the vascular media, physiologic stress is manifested as cyclic strain, while in the lumen, cells are subjected to shear stress. These two respective biomechanical forces influence the phenotype and degree of differentiation or proliferation of smooth muscle cells and endothelial cells within the human vasculature. Elucidation of the effect of these mechanical forces on cellular differentiation has led to a surge of research into this area because of the implications for both the treatment of atherosclerotic disease and the future of vascular tissue engineering. The use of mechanical force to directly control vascular cell differentiation may be utilized as an invaluable engineering tool in the future. However, an understanding of the role of hemodynamics in vascular cell differentiation and proliferation is critical before application can be realized. Thus, this review will provide a current perspective on the latest research and controversy behind the role of hemodynamic forces for vascular cell differentiation and phenotype modulation. Furthermore, this review will illustrate the application of hemodynamic force for vascular tissue engineering and explicate future directions for research.
In spite of an elevation in PT-INR, patients undergoing a liver resection demonstrated a brief hypercoagulable state, followed by normal coagulation function based on TEG. These data call into question the practice of utilizing PT-INR to guide plasma transfusion and timing of prophylactic anticoagulation after a liver resection.
As the prevalence of vascular disease has continued to expand, the need for a suitable arterial replacement has prompted researchers to look beyond synthetic and autologous grafts toward the field of tissue engineering. Advances in vascular tissue engineering have utilized both mesenchymal and hematopoietic stem cells as a cell source in an attempt to create a fully engineered small-diameter graft. Stem cells offer enormous potential as a cell source because of their proliferative and growth potential, and the application of stem cell technology has far-reaching implications for future applications. The innovative use of stem cells for vascular tissue engineering has opened new possibilities for a fully engineered blood vessel. The purpose of this review is to summarize the current perspective on the use of stem cells for vascular tissue engineering. It focuses principally on the classes of stem cells used, techniques for differentiation scaffolding technology, and the successes and failures of models.
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