药代动力学实验装置系统

药代动力学实验装置系统，flexcell str4000，美国Flexcell公司，专注于细胞力学培养产品的设计和制造30多年。其体外细胞拉应力、压应力和流体剪切应力加载刺激系统以及配套的培养板、硅胶膜载片等耗材*。其产品成熟度高、成功应用文献量达4000多篇，国内有100多家单位使用，无技术风险和使用风险，已成为细胞力学体外加载模型的黄金标准，是细胞组织力学研究者的shou选

药代动力学实验装置系统，flexcell str4000，

美国Flexcell公司，专注于细胞力学培养产品的设计和制造30多年。其体外细胞拉应力、压应力和流体剪切应力加载刺激系统以及配套的培养板、硅胶膜载片等耗材*。其产品成熟度高、成功应用文献量达4000多篇，国内有100多家单位使用，无技术风险和使用风险，已成为细胞力学体外加载模型的黄金标准，是细胞组织力学研究者的shou选

为细胞提供各种形式的流体切应力：稳流式切应力，脉冲式切应力或者往返式切应力。

在经过特殊基质蛋白包被的25mm x 75mm x 1.0mm 细胞培养载片上培养细胞。

计算机控制的蠕动泵可以调节切应力的大小，从0-35 dynes/cm².

通过Osci-Flow液体控制仪提供往返式或者脉冲式的流体切应力。

检测细胞在液流作用下的排列反应。

设备易拆卸并可高温消毒。

可以在经过特殊包被的6个细胞培养载片上同时培养细胞。

可以在提供流体切应力的同时抻拉细胞，测试血管和结绨组织细胞对液体流动的实时反应。

为培育在StageFlexer硅胶模表面或者基质蛋白包被的细胞培养片上的细胞提供切应力。
使用FX-5000T应力加载系统抻拉细胞，并且可以在实验前，实验中或者实验后提供切应力。
计算机控制蠕动泵，调节切应力大小，从0-35 dynes/cm². 
使用标准正立式显微镜实时观察细胞在切应力下的反应。
检测细胞在流体作用下的排列反应。
检测在液体切应力下各种激活剂/抑制剂对细胞反应的影响。
使用荧光团例如FURA-2检测细胞内[Ca2+]ic或者其它离子对切应力的反应。

典型应用文献：

1. Archambault JM, Elfervig MK, Tsuzaki M, Herzog W, Banes AJ. Shear stress response of rabbit tendon cells is serum dependent. Proceedings of the Eleventh Canadian Society for Biomechanics Conference, 181, 2000.
2. Archambault JM, Elfervig-Wall MK, Tsuzaki M, Herzog W, Banes AJ. Rabbit tendon cells produce MMP-3 in response to fluid flow without significant calcium transients. J Biomech 35(3):303-309, 2002.

3. Clark PR, Jensen TJ, Kluger MS, Morelock M, Hanidu A, Qi Z, Tatake RJ, Pober JS. MEK5 is activated by shear stress, activates ERK5 and induces KLF4 to modulate TNF responses in human dermal microvascular endothelial cells. Microcirculation 18(2):102-117, 2011.
4. de Castro LF, Maycas M, Bravo B, Esbrit P, Gortazar A. VEGF receptor 2 (VEGFR2) activation is essential for osteocyte survival induced by mechanotransduction. J Cell Physiol 230(2):278-85, 2015.
5. Eifler RL, Blough ER, Dehlin JM, Haut Donahue TL. Oscillatory fluid flow regulates glycosaminoglycan production via an intracellular calcium pathway in meniscal cells. J Orthop Res 24(3):375-384, 2006.
6. Elfervig M, Francke E, Archambault J, Herzog W, Tsuzaki M, Bynum D, Brown TD, Banes AJ. Fluid-induced shear stress activates human tendon cells to signal through multiple Ca2+ dependent pathways [abstract]. Transactions of the 46th Annual Meeting of the Orthopaedic Research Society 25:179, 2000.
7. Elfervig M, Lotano M, Tsuzaki M, Faber J, Banes A J. Fluid-induced shear stress modulates Cx-43 expression in avian tendon cells but does not induce a Ca2+ signal [abstract]. Transactions of the 47th Annual Meeting of the Orthopaedic Research Society 26:570, 2001.
8. Elfervig MK, Minchew JT, Francke E, Tsuzaki M, Banes AJ. IL-1 sensitizes intervertebral disc annulus cells to fluid-induced shear stress. J Cell Biochem 82(2):290-298, 2001.
9. Finley MJ, Rauova L, Alferiev IS, Weisel JW, Levy RJ, Stachelek SJ. Diminished adhesion and activation of platelets and neutrophils with CD47 functionalized blood contacting surfaces. Biomaterials 33(24):5803-5811, 2012.
10. Francke E, Banes A, Elfervig M, Brown T, Bynum D. Fluid-induced shear stress increases [Ca2+]ic in cultured human tendon epitenon cells [abstract]. Transactions of the 46th Annual Meeting of the Orthopaedic Research Society 25:638, 2000.
11. Francke E, Elfervig MK, Sood A, Brown TD, Bynum DK, Banes AJ. Fluid-induced shear stress stimulates Ca2+ signaling in human epitenon cells [abstract]. 1999 Advances in Bioengineering, J.S. Wayne, ed. American Society of Mechanical Engineers: New York, 1999.
12. Gao X, Wu L, O'Neil RG. Temperature-modulated diversity of TRPV4 channel gating: activation by physical stresses and phorbol ester derivatives through protein kinase C-dependent and -independent pathways. J Biol Chem 278(29):27129-27137, 2003.
13. Ge C, Song J, Chen L, Wang L, Chen Y, Liu X, Zhang Y, Zhang L, Zhang M. Atheroprotective pulsatile flow induces ubiquitin-proteasome-mediated degradation of programmed cell death 4 in endothelial cells. PLoS One 9(3):e91564, 2014.
14. Glossop JR, Hidalgo-Bastida LA, Cartmell SH. Fluid shear stress induces differential gene expression of leukemia inhibitory factor in human mesenchymal stem cells. J Biomat Tiss Eng 1:166-176, 2011.
15. Gortazar AR, Martin-Millan M, Bravo B, Plotkin LI, Bellido T. Crosstalk between caveolin-1/extracellular signal-regulated kinase (ERK) and β-catenin survival pathways in osteocyte mechanotransduction. J Biol Chem 288(12):8168-8175, 2013.
16. Grabias BM, Konstantopoulos K. Epithelial-mesenchymal transition and fibrosis are mutually exclusive reponses in shear-activated proximal tubular epithelial cells. FASEB J 26(10):4131-41, 2012.
17. Guan PP, Yu X, Guo JJ, Wang Y, Wang T, Li JY, Konstantopoulos K, Wang ZY, Wang P. By activating matrix metalloproteinase-7, shear stress promotes chondrosarcoma cell motility, invasion and lung colonization. Oncotarget 6(11):9140-59, 2015.
18. Hamamura K, Zhang P, Zhao L, Shim JW, Chen A, Dodge TR, Wan Q, Shih H, Na S, Lin CC, Sun HB, Yokota H. Knee loading reduces MMP13 activity in the mouse cartilage. BMC Musculoskelet Disord 14(1):312, 2013.
19. Hosoya T, Maruyama A, Kang MI, Kawatani Y, Shibata T, Uchida K, Warabi E, Noguchi N, Itoh K, Yamamoto M. Differential responses of the Nrf2-Keap1 system to laminar and oscillatory shear stresses in endothelial cells. J Biol Chem 280(29):27244-27250, 2005.
20. Jaitovich A, Mehta S, Na N, Ciechanover A, Goldman RD, Ridge KM. Ubiquitin-proteasome-mediated degradation of keratin intermediate filaments in mechanically stimulated A549 cells. J Biol Chem 283(37):25348-25355, 2008.
21. Kamel MA, Picconi JL, Lara-Castillo N, Johnson ML. Activation of β-catenin signaling in MLO-Y4 osteocytic cells versus 2T3 osteoblastic cells by fluid flow shear stress and PGE2: implications for the study of mechanosensation in bone. Bone 47(5):872-881, 2010.
22. Lee CY, Hsu HC, Zhang X, Wang DY, Luo ZP. Cyclic compression and tension regulate differently the metabolism of chondrocytes. J Musculoskeletal Res 9(2):59-64, 2005.

23. Li M, Liu X, Zhang Y, Di M, Wang H, Wang L, Chen Y, Liu X, Cao X, Zeng R, Zhang Y, Zhang M. Upregulation of Dickkopf1 by oscillatory shear stress accelerates atherogenesis. J Mol Med (Berl) 94(4):431-41, 2016.
24. Liao C, Cheng T, Wang S, Zhang C, Jin L, Yang Y. Shear stress inhibits IL-17A-mediated induction of osteoclastogenesis via osteocyte pathways. Bone 101:10-20, 2017.
25. Liu J, Bi X, Chen T, Zhang Q, Wang SX, Chiu JJ, Liu GS, Zhang Y, Bu P, Jiang F. Shear stress regulates endothelial cell autophagy via redox regulation and Sirt1 expression. Cell Death Dis 6:e1827, 2015.
26. Malone AM, Batra NN, Shivaram G, Kwon RY, You L, Kim CH, Rodriguez J, Jair K, Jacobs CR. The role of actin cytoskeleton in oscillatory fluid flow-induced signaling in MC3T3-E1 osteoblasts. Am J Physiol Cell Physiol 292(5):C1830-C1836, 2007.
27. Maycas M, Ardura JA, de Castro LF, Bravo B, Gortázar AR, Esbrit P. Role of the parathyroid hormone type 1 receptor (PTH1R) as a mechanosensor in osteocyte survival. J Bone Miner Res 30(7):1231-44, 2015.
28. Maycas M, Bravo-Molina B, Fernández de Castro L, Pozuelo JM, Forriol F, P Esbrit, Rodríguez de Gortázar A. High glucose alters the antiapoptotic response to mechanical stimulation in MLO-Y4 osteocytic cells. Trauma Fund MAPFRE 25(2):97-100, 2014.
29. Metaxa E, Meng H, Kaluvala SR, Szymanski MP, Paluch RA, Kolega J. Nitric oxide-dependent stimulation of endothelial cell proliferation by sustained high flow. Am J Physiol Heart Circ Physiol 295(2):H736-H742, 2008.
30. Ni J, Waldman A, Khachigian LM. c-Jun regulates shear- and injury-inducible Egr-1 expression, vein graft stenosis after autologous end-to-side transplantation in rabbits, and intimal hyperplasia in human saphenous veins. J Biol Chem 285(6):4038-4048, 2010.
31. Qi J, Chi L, Faber J, Koller B, Banes AJ. ATP reduces gel compaction in osteoblast-populated collagen gels. J Appl Physiol 102(3):1152-60, 2007.
32. Radel C, Carlile-Klusacek M, Rizzo V. Participation of caveolae in 1 integrin-mediated mechanotransduction. Biochem Biophys Res Commun 358(2):626-631, 2007.
33. Radel C, Rizzo V. Integrin mechanotransduction stimulates caveolin-1 phosphorylation and recruitment of Csk to mediate actin reorganization. Am J Physiol Heart Circ Physiol 288(2):H936-H945, 2005.
34. Ridge KM, Linz L, Flitney FW, Kuczmarski ER, Chou YH, Omary MB, Sznajder JI, Goldman RD. Keratin 8 phosphorylation by protein kinase C  regulates shear stress-mediated disassembly of keratin intermediate filaments in alveolar epithelial cells. J Biol Chem 280(34):30400-30405, 2005.
35. Riehl BD, Lee JS, Ha L, Kwon IK, Lim JY. Flowtaxis of osteoblast migration under fluid shear and the effect of RhoA kinase silencing. PLoS One 12(2):e0171857, 2017.
36. Riehl BD, Lee JS, Ha L, Lim JY. Fluid-flow-induced mesenchymal stem cell migration: role of focal adhesion kinase and RhoA kinase sensors. J R Soc Interface 12(107), 2015. pii: 20150300.
37. Rosser J, Bonewald LF. Studying osteocyte function using the cell lines MLO-Y4 and MLO-A5. Methods Mol Biol 816:67-81, 2012.
38. Shim JW, Hamamura K, Chen A, Wan Q, Na S, Yokota H. Rac1 mediates load-driven attenuation of mRNA expression of nerve growth factor  in cartilage and chondrocytes. J Musculoskelet Neuronal Interact 13(3):372-9, 2013.
39. Siu KL, Gao L, Cai H. Differential roles of /NOXO1 and NOX2/p47phox in mediating endothelial redox responses to oscillatory and unidirectional laminar shear stress. J Biol Chem 291(16):8653-62, 2016.
40. Sivaramakrishnan S, DeGiulio JV, Lorand L, Goldman RD, Ridge KM. Micromechanical properties of keratin intermediate filament networks. PNAS 105(3):889-894, 2008.
41. Sivaramakrishnan S, Schneider JL, Sitikov A, Goldman RD, Ridge KM. Shear stress induced reorganization of the keratin intermediate filament network requires phosphorylation by protein kinase C . Mol Biol Cell 20(11):2755-2765, 2009.
42. Spatz JM, Wein MN, Gooi JH, Qu Y, Garr JL, Liu S, Barry KJ, Uda Y, Lai F, Dedic C, Balcells-Camps M, Kronenberg HM, Babij P, Pajevic PD. The Wnt inhibitor sclerostin is up-regulated by mechanical unloading in osteocytes in vitro. J Biol Chem 290(27):16744-58, 2015.
43. Srivastava T, McCarthy ET, Sharma R, Cudmore PA, Sharma M, Johnson ML, Bonewald LF. Prostaglandin E(2) is crucial in the response of podocytes to fluid flow shear stress. J Cell Commun Signal 4(2):79-90, 2010.
44. Stachelek SJ, Alferiev I, Connolly JM, Sacks M, Hebbel RP, Bianco R, Levy RJ. Cholesterol-modified polyurethane valve cusps demonstrate blood outgrowth endothelial cell adhesion post-seeding in vitro and in vivo. Ann Thorac Surg 81(1):47-55, 2006.
FLEXCELL® INTERNATIONAL CORPORATION
76
45. Sun HB, Liu Y, Qian L, Yokota H. Model-based analysis of matrix metalloproteinase expression under mechanical shear. Ann Biomed Eng 31(2):171-180, 2003.
46. Takai E, Landesberg R, Katz RW, Hung CT, Guo XE. Substrate modulation of osteoblast adhesion strength, focal adhesion kinase activation, and responsiveness to mechanical stimuli. Mol Cell Biomech 3(1):1-12, 2006.
47. Thaler JD, Achari Y, Lu T, Shrive NG, Hart DA. Estrogen receptor  and truncated variants enhance the expression of transfected MMP-1 promoter constructs in response to specific mechanical loading. Biology of Sex Differences 5:14, 2014.
48. Tran J, Magenau A, Rodriguez M, Rentero C, Royo T, Enrich C, Thomas SR, Grewal T, Gaus K. Activation of endothelial nitric oxide (eNOS) occurs through different membrane domains in endothelial cells. PLoS One 11(3):e0151556, 2016.
49. Wang XL, Fu A, Spiro C, Lee HC. Proteomic analysis of vascular endothelial cells-effects of laminar shear stress and high glucose. J Proteomics Bioinform 2:445, 2009.
50. Wang P, Guan PP, Wang T, Yu X, Guo JJ, Konstantopoulos K, Wang ZY. Interleukin-1β and cyclic AMP mediate the invasion of sheared chondrosarcoma cells via a matrix metalloproteinase-1-dependent mechanism. Biochim Biophys Acta 1843(5):923-33, 2014.
51. Wang P, Zhu F, Konstantopoulos K. The antagonistic actions of endogenous interleukin-1β and 15-deoxy-12,14-prostaglandin J2 regulate the temporal synthesis of matrix metalloproteinase-9 in sheared chondrocytes. J Biol Chem 287(38):31877-93, 2012.
52. Wang P, Zhu F, Lee NH, Konstantopoulos K. Shear-induced interleukin-6 synthesis in chondrocytes: roles of E prostanoid (EP) 2 and EP3 in cAMP/protein kinase A- and PI3-K/Akt-dependent NF-B activation. J Biol Chem 285(32):24793-24804, 2010.
53. Wu L, Gao X, Brown RC, Heller S, O'Neil RG. Dual role of the TRPV4 channel as a sensor of flow and osmolality in renal epithelial cells. Am J Physiol Renal Physiol 293(5):F1699-F1713, 2007.
54. Yang B, Rizzo V. Shear stress activates eNOS at the endothelial apical surface through β1 containing integrins and caveolae. Cell Mol Bioeng 6(3):346-354, 2013.
55. Yang W, Lu Y, Kalajzic I, Guo D, Harris MA, Gluhak-Heinrich J, Kotha S, Bonewald LF, Feng JQ, Rowe DW, Turner CH, Robling AG, Harris SE. Dentin matrix protein 1 gene cis-regulation: use in osteocytes to characterize local responses to mechanical loading in vitro and in vivo. J Biol Chem 280(21):20680-20690, 2005.
56. Yokota H, Goldring MB, Sun HB. CITED2-mediated regulation of MMP-1 and MMP-13 in human chondrocytes under flow shear. J Biol Chem 278(47):47275-47280, 2003.
57. Yoo PS, Mulkeen AL, Dardik A, Cha CH. A novel in vitro model of lymphatic metastasis from colorectal cancer. J Surg Res 143(1):94-98, 2007.
58. Zhang J, Zhang HY, Zhang M, Qiu ZY, Wu YP, Callaway DA, Jiang JX, Lu L, Jing L, Yang T, Wang MQ. Connexin43 hemichannels mediate small molecule exchange between chondrocytes and matrix in biomechanically-stimulated temporomandibular joint cartilage. Osteoarthritis Cartilage 22(6):822-30, 2014.
59. Zhang K, Barragan-Adjemian C, Ye L, Kotha S, Dallas M, Lu Y, Zhao S, Harris M, Harris SE, Feng JQ, Bonewald LF. E11/gp38 selective expression in osteocytes: regulation by mechanical strain and role in dendrite elongation. Mol Cell Biol 26(12):4539-45, 2006.
60. Zhu F, Wang P, Kontrogianni-Konstantopoulos A, Konstantopoulos K. Prostaglandin (PG)D(2) and 15-deoxy-(12,14)-PGJ(2), but not PGE(2), mediate shear-induced chondrocyte apoptosis via protein kinase A-dependent regulation of polo-like kinases. Cell Death Differ 17(8):1325-1334, 2010.
61. Zhu F, Wang P, Lee NH, Goldring MB, Konstantopoulos K. Prolonged application of high fluid shear to chondrocytes recapitulates gene expression profiles associated with osteoarthritis. PLoS One 5(12):e15174, 2010.