A biophysical indicator of vaso-occlusive risk in sickle cell disease.
A biophysical indicator of vaso-occlusive risk in sickle cell disease.
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DOI：
10.1126/scitranslmed.3002738
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发表时间：
2012-02-29
影响因子：
17.1
通讯作者：
Bhatia SN
中科院分区：
文献类型：
--
作者：
Wood DK;Soriano A;Mahadevan L;Higgins JM;Bhatia SN
对疾病的预测性生物标志物的研究主要集中在分子指标上;然而，机械和生物物理标志物可以整合长度尺度上的多个途径，可以提供潜在病理生理学的更全面的图景。镰状细胞病是第一种被破译其分子起源的疾病，影响着全世界数百万人，自其最初被描述以来，世纪来一直在分子、细胞、组织和生物体水平上进行深入研究。然而，仍然有很少的，如果有的话，标志物，使我们能够表征这种疾病的严重程度。由于镰状细胞病的并发症主要是由于血管闭塞事件，我们假设，表征血管闭塞过程的物理指标可以作为疾病严重程度的标志。在这里，我们使用一个简单的微流体装置来表征在生理相关条件下的堵塞的动态，使用突然脱氧事件后的流动阻力的变化率。我们的研究表明，与现有的实验室检查不同，这个单一的生物物理参数可用于区分具有不同临床结果的患者。我们的测定提供了疾病严重程度的生物物理标志物，可用于指导临床干预的时机，监测疾病的进展，并在体外环境中测量药物反应，输血和新型小分子的疗效。
The search for predictive biomarkers of disease has largely focused on molecular indicators; however, mechanical and biophysical markers, which can integrate multiple pathways across length scales, may provide a more global picture of the underlying pathophysiology. Sickle cell disease, the first disease to have its molecular origins decoded, affects millions of people worldwide and has been studied intensively at the molecular, cellular, tissue and organismal level for a century since its initial description. However, there are still few, if any, markers that allow us to characterize the severity of this disease. Because the complications of sickle cell disease are largely due to vaso-occlusive events, we hypothesized that a physical metric characterizing the vaso-occlusive process could serve as a marker of disease severity. Here we use a simple microfluidic device to characterize the dynamics of jamming in physiologically relevant conditions, using the rate of change of the resistance to flow following a sudden deoxygenation event. Our studies show that this single biophysical parameter could be used to distinguish between patients with divergent clinical outcomes, unlike existing laboratory tests. Our assay provides a biophysical marker of disease severity that could be used to guide timing of clinical interventions, to monitor the progression of the disease, and to measure the efficacy of drug response, transfusion, and novel small molecules in an in vitro setting.
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影响因子：
6.5
作者：
Abdulmalik, O;Safo, MK;Asakura, T
通讯作者：
Asakura, T
影响因子：
--
作者：
Eaton, W A;Hofrichter, J
通讯作者：
Hofrichter, J
影响因子：
2.4
作者：
Embury, SH
通讯作者：
Embury, SH
DOI：
10.1073/pnas.0707122105
发表时间：
2007-12-18
影响因子：
11.1
作者：
Higgins, J. M.;Eddington, D. T.;Mahadevan, L.
通讯作者：
Mahadevan, L.
影响因子：
64.8
作者：
Karnoub, Antoine E.;Dash, Ajeeta B.;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.