37 research outputs found

    Fluid shear stress modulation of hepatocyte like cell function

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    Freshly isolated human adult hepatocytes are considered to be the gold standard tool for in vitro studies. However, primary hepatocyte scarcity, cell cycle arrest and the rapid loss of cell phenotype limit their widespread deployment. Human embryonic stem cells and induced pluripotent stem cells provide renewable sources of hepatocyte-like cells (HLCs). Despite the use of various differentiation methodologies, HLCs like primary human hepatocytes exhibit unstable phenotype in culture. It has been shown that the functional capacity can be improved by adding back elements of human physiology, such as cell co-culture or through the use of natural and/or synthetic surfaces. In this study, the effect of fluid shear stress on HLC performance was investigated. We studied two important liver functions, cytochrome P450 drug metabolism and serum protein secretion, in static cultures and those exposed to fluid shear stress. Our study demonstrates that fluid shear stress improved Cyp1A2 activity by approximately fivefold. This was paralleled by an approximate ninefold increase in sensitivity to a drug, primarily metabolised by Cyp2D6. In addition to metabolic capacity, fluid shear stress also improved hepatocyte phenotype with an approximate fourfold reduction in the secretion of a foetal marker, alpha-fetoprotein. We believe these studies highlight the importance of introducing physiologic cues in cell-based models to improve somatic cell phenotype

    Apicobasal polarity of brain endothelial cells

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    Impaired retinal microcirculation in multiple sclerosis

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    BACKGROUND: The transparent ocular structure enables quantitative analysis of microvasculature of retina, a neuronal tissue affected by multiple sclerosis. OBJECTIVE: To determine whether the retinal blood flow velocity and flow volume at the macula are impaired in patients with relapsing remitting multiple sclerosis (RRMS). METHODS: Seventeen RRMS patients and 17 age- and gender-matched healthy subjects were assessed. A Retinal Function Imager was used to measure the blood flow velocity of retinal arterioles and venules, and to calculate the total perifoveal blood flow volume. RESULTS: The blood flow velocities of the retinal arterioles (3.34 ± 0.89 mm/s) and venules (2.61 ± 0.6 mm/s) were significantly lower in MS patients than normal subjects (arteriole: 4.10 ± 0.87 mm/s; venule: 3.22 ± 0.65 mm/s, both P = 0.01). In addition, the total perifoveal blood flow volume in arterioles (3.74 ± 1.64 nl/s) and venules (3.81 ± 1.60 nl/s) were significantly lower in MS patients than in normal subjects (arteriole: 4.87 ± 1.41 nl/s, P = 0.02; venule: 4.71 ± 1.64 nl/s, P = 0.04). CONCLUSION: The impaired retinal microcirculation in RRMS patients indicates microvascular dysfunction in MS
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