An in-vitro cell culture system for accurately reproducing the coupled hemodynamic signals at the artery endothelium

• Autorzy: Liang Lixue , Wang Xueying , Chen Dong , Wang Yanxia , Luo Xiaoyue , Liu Bo , Wang Yu , Qin Kai-rong

Identyfikatory

DOI

10.1016/j.bbe.2024.08.001

• Języki publikacji: EN

Abstrakty

EN

Microfluidics has been an effective technology to reconstruct the in-vivo physiological hemodynamic microenvironment, which is significantly important for preventing and curing circulatory system-related diseases. However, these existing microfluidic systems have failed to accurately reproduce the arterial blood pressure, shear stress, circumferential strain, as well as their coupling relationship, and have not taken into account whether the cells at various locations in the culture chamber are subjected to consistent mechanical stimulation. To solve the above shortcomings, this study developed an in-vitro endothelial cell culture system (ECCS) containing a microfluidic chip and afterload components based on the hemodynamic principles to reappear the desired hemodynamic signals and their coupling relationship accurately, while a relatively uniform area of stress and strain distribution was selected in the microfluidic chip for a more reliable cell mechanobiology study. The sensitivity of global hemodynamic behaviors of the ECCS was analyzed, and numerical simulation and in-vitro experiments were implemented to verify the performance of the proposed ECCS. Finally, the cellular hemodynamic response was tested using human umbilical vein endothelial cells, demonstrating that the proposed in-vitro ECCS has better biological effectiveness. In general, the proposed ECCS in this study provided a more accurate and reliable tool for reproducing the in-vivo hemodynamic microenvironment and showed good potential in the mechanobiology study.

Słowa kluczowe

EN

endothelial cell culture system; microfluidic chip; in vitro; hemodynamics

• Wydawca: Nałęcz Institute of Biocybernetics and Biomedical Engineering of the Polish Academy of Sciences ; Elsevier
• Czasopismo: Biocybernetics and Biomedical Engineering
• Rocznik: 2024
• Tom: Vol. 44, no. 3
• Strony: 501--512
• Opis fizyczny: Bibliogr. 40 poz., rys., wykr.

Twórcy

autor

Liang Lixue

• Institute of Cardio-Cerebrovascular Medicine, Central Hospital of Dalian University of Technology, Dalian 116024, Liaoning Province, PR China
• School of Mechanical Engineering, Dalian University of Technology, Dalian 116024, Liaoning Province, PR China

autor

Wang Xueying

• School of Optoelectronic Engineering and Instrumentation Science, Dalian University of Technology, Dalian 116024, Liaoning Province, PR China

autor

Chen Dong

• Institute of Cardio-Cerebrovascular Medicine, Central Hospital of Dalian University of Technology, Dalian 116024, Liaoning Province, PR China

autor

Wang Yanxia

• School of Rehabilitation Medicine, Shandong Second Medical University, Weifang 261042, Shandong Province, PR China

autor

Luo Xiaoyue

• School of Optoelectronic Engineering and Instrumentation Science, Dalian University of Technology, Dalian 116024, Liaoning Province, PR China

autor

Liu Bo

• School of Biomedical Engineering, Faculty of Medicine, Dalian University of Technology, Dalian 116024, Liaoning Province, PR China

autor

Wang Yu

• Institute of Cardio-Cerebrovascular Medicine, Central Hospital of Dalian University of Technology, Dalian 116024, Liaoning Province, PR China
• School of Biomedical Engineering, Faculty of Medicine, Dalian University of Technology, Dalian 116024, Liaoning Province, PR China

autor

Qin Kai-rong

• Institute of Cardio-Cerebrovascular Medicine, Central Hospital of Dalian University of Technology, Dalian 116024, Liaoning Province, PR China
• School of Biomedical Engineering, Faculty of Medicine, Dalian University of Technology, Dalian 116024, Liaoning Province, PR China

Bibliografia

• [1] Chien S. Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell. Am J Physiol-Heart Circul Physiol 2007;292:H1209-24. https://doi.org/10.1152/ajpheart.01047.2006.
• [2] Han Y, Huang K, Yao Q-P, Jiang Z-L. Mechanobiology in vascular remodeling. Natl Sci Rev 2018;5:933-46. https://doi.org/10.1093/nsr/nwx153.
• [3] He L, Zhang C-L, Chen Q, Wang L, Huang Y. Endothelial shear stress signal transduction and atherogenesis: From mechanisms to therapeutics. Pharmacol Ther 2022;235:108152. https://doi.org/10.1016/j.pharmthera.2022.108152.
• [4] Yu J, Fu J, Zhang X, Cui X, Cheng M. The integration of metabolomic and proteomic analyses revealed alterations in inflammatory-related protein metabolites in endothelial progenitor cells subjected to oscillatory shear stress. Front Physiol 2022;13:825966. https://doi.org/10.3389/fphys.2022.825966.
• [5] Fischer L, Nosratlo M, Hast K, Karakaya E, Str¨ohlein N, Esser TU, et al. Calcium supplementation of bioinks reduces shear stress-induced cell damage during bioprinting. Biofabrication 2022;14:045005. https://doi.org/10.1088/1758-5090/ac84af.
• [6] Wang Y-X, Liu H-B, Li P-S, Yuan W-X, Liu B, Liu S-T, et al. ROS and NO dynamics in endothelial cells exposed to exercise-induced wall shear stress. Cell Mol Bioeng 2019;12:107-20. https://doi.org/10.1007/s12195-018-00557-w.
• [7] Xue C-D, Li Y-J, Na J-T, Wang Y-X, Yu H-J, Liu B, et al. A microfluidic platform enabling real-time control of dynamic biochemical stimuli to biological cells. J Micromech Microeng 2020;30:095011. https://doi.org/10.1088/1361-6439/ab9e4e.
• [8] Jones TJ, Nauli SM. Mechanosensory calcium signaling. Adv Exp Med Biol 2012; 740:1001-15. https://doi.org/10.1007/978-94-007-2888-2_46.
• [9] Surya VN, Michalaki E, Fuller GG, Dunn AR. Lymphatic endothelial cell calcium pulses are sensitive to spatial gradients in wall shear stress. Mol Biol Cell 2019;30: 923-31. https://doi.org/10.1091/mbc.E18-10-0618.
• [10] Selahi A, Chakraborty S, Muthuchamy M, Zawieja DC, Jain A. Intracellular calcium dynamics of lymphatic endothelial and muscle cells co-cultured in a Lymphangion-Chip under pulsatile flow. Analyst 2022;147:2953-65. https://doi.org/10.1039/ D2AN00396A.
• [11] Tian S, Cai Z, Sen P, Van Uden D, Van De Kamp E, Thuillet R, et al. Loss of lung microvascular endothelial Piezo2 expression impairs NO synthesis, induces EndMT, and is associated with pulmonary hypertension. Am J Physiol-Heart Circul Physiol 2022;323:H958-74. https://doi.org/10.1152/ajpheart.00220.2022.
• [12] Pan S. Molecular mechanisms responsible for the atheroprotective effects of laminar shear stress. Antioxid Redox Signal 2009;11:1669-82. https://doi.org/10.1089/ars.2009.2487.
• [13] Han Y, Wang L, Yao Q-P, Zhang P, Liu B, Wang G-L, et al. Nuclear envelope proteins Nesprin2 and LaminA regulate proliferation and apoptosis of vascular endothelial cells in response to shear stress. Biochim Biophys Acta-Mol Cell Res 2015;1853:1165-73. https://doi.org/10.1016/j.bbamcr.2015.02.013.
• [14] Escuer J, Martínez MA, McGinty S, Peña E. Mathematical modelling of the restenosis process after stent implantation. J R Soc Interface 2019;16:20190313. https://doi.org/10.1098/rsif.2019.0313.
• [15] Latorre M, Humphrey JD. Mechanobiological stability of biological soft tissues. J Mech Phys Solids 2019;125:298-325. https://doi.org/10.1016/j.jmps.2018.12.013.
• [16] Schwartz MA, Chen CS. Deconstructing dimensionality. Science 2013;339:402-4. https://doi.org/10.1126/science.1233814.
• [17] Blackman BR, García-Cardeña G, Gimbrone MA. A new in vitro model to evaluate differential responses of endothelial cells to simulated arterial shear stress waveforms. J Biomech Eng 2002;124:397-407. https://doi.org/10.1115/1.1486468.
• [18] Chin LK, Yu JQ, Fu Y, Yu T, Liu AQ, Luo KQ. Production of reactive oxygen species in endothelial cells under different pulsatile shear stresses and glucose concentrations. Lab Chip 2011;11:1856. https://doi.org/10.1039/c0lc00651c.
• [19] Sinha R, Le Gac S, Verdonschot N, Van Den Berg A, Koopman B, Rouwkema J. A medium throughput device to study the effects of combinations of surface strains and fluid-flow shear stresses on cells. Lab Chip 2015;15:429-39. https://doi.org/10.1039/C4LC01259C.
• [20] Lee J, Estlack Z, Somaweera H, Wang X, Lacerda CMR, Kim J. A microfluidic cardiac flow profile generator for studying the effect of shear stress on valvular endothelial cells. Lab Chip 2018;18:2946-54. https://doi.org/10.1039/C8LC00545A.
• [21] Hu C, Chen Y, Tan MJA, Ren K, Wu H. Microfluidic technologies for vasculature biomimicry. Analyst 2019;144:4461-71. https://doi.org/10.1039/C9AN00421A.
• [22] Arora S, Lam AJY, Cheung C, Yim EKF, Toh Y. Determination of critical shear stress for maturation of human pluripotent stem cell-derived endothelial cells towards an arterial subtype. Biotechnol Bioeng 2019;116:1164-75. https://doi.org/10.1002/bit.26910.
• [23] Zheng W, Jiang B, Wang D, Zhang W, Wang Z, Jiang X. A microfluidic flow-stretch chip for investigating blood vessel biomechanics. Lab Chip 2012;12:3441. https://doi.org/10.1039/c2lc40173h.
• [24] Meza D, Abejar L, Rubenstein DA, Yin W. A shearing-stretching device that can apply physiological fluid shear stress and cyclic stretch concurrently to endothelial cells. J Biomech Eng 2016;138:031007. https://doi.org/10.1115/1.4032550.
• [25] Chu P-Y, Hsieh H-Y, Chung P-S, Wang P-W, Wu M-C, Chen Y-Q, et al. Development of vessel mimicking microfluidic device for studying mechano-response of endothelial cells. iScience 2023;26:106927. https://doi.org/10.1016/j.isci.2023.106927.
• [26] Aboelkassem Y, Savic D. Particle swarm optimizer for arterial blood flow models. Comput Meth Programs Biomed 2021;201:105933. https://doi.org/10.1016/j.cmpb.2021.105933.
• [27] Na J-T, Xue C-D, Wang Y-X, Li Y-J, Wang Y, Liu B, et al. Fabricating a multicomponent microfluidic system for exercise-induced endothelial cell mechanobiology guided by hemodynamic similarity. Talanta 2023;253:123933. https://doi.org/10.1016/j.talanta.2022.123933.
• [28] Estrada R, Giridharan GA, Nguyen M-D, Roussel TJ, Shakeri M, Parichehreh V, et al. Endothelial cell culture model for replication of physiological profiles of pressure, flow, stretch, and shear stress in vitro. Anal Chem 2011;83:3170-7. https://doi.org/10.1021/ac2002998.
• [29] Ives CL, Eskin SG, McIntire LV. Mechanical effects on endothelial cell morphology: In vitro assessment. In Vitro Cell Dev Biol 1986;22:500-7. https://doi.org/10.1007/BF02621134.
• [30] Hishikawa K, Lüscher TF. Pulsatile stretch stimulates superoxide production in human aortic endothelial cells. Circulation 1997;96:3610-6. https://doi.org/10.1161/01.CIR.96.10.3610.
• [31] Chien S, Li S, Shyy J-Y-J. Effects of mechanical forces on signal transduction and gene expression in endothelial cells. Hypertension 1998;31:162-9. https://doi.org/10.1161/01.HYP.31.1.162.
• [32] Kakisis JD, Liapis CD, Sumpio BE. Effects of cyclic strain on vascular cells. Endothelium 2004;11:17-28. https://doi.org/10.1080/10623320490432452.
• [33] Gervais T, El-Ali J, Günther A, Jensen KF. Flow-induced deformation of shallow microfluidic channels. Lab Chip 2006;6:500. https://doi.org/10.1039/b513524a.
• [34] Son Y. Determination of shear viscosity and shear rate from pressure drop and flow rate relationship in a rectangular channel. Polymer 2007;48:632-7. https://doi.org/10.1016/j.polymer.2006.11.048.
• [35] Hardy BS, Uechi K, Zhen J, Pirouz KH. The deformation of flexible PDMS microchannels under a pressure driven flow. Lab Chip 2009;9:935-8. https://doi.org/10.1039/B813061B.
• [36] Dessalles CA, Ramón-Lozano C, Babataheri A, Barakat AI. Luminal flow actuation generates coupled shear and strain in a microvessel-on-chip. Biofabrication 2022; 14:015003. https://doi.org/10.1088/1758-5090/ac2baa.
• [37] Naumov AY, Balashov SA, Melkumyants AM. Use of input impedance to determine changes in the resistance of arterial vessels at different levels in feline femoral bed. Ann Biomed Eng 2014;42:1644-57. https://doi.org/10.1007/s10439-014-1016-6.
• [38] Na J-T, Hu S-Y, Xue C-D, Wang Y-X, Chen K-J, Li Y-J, et al. A microfluidic system for precisely reproducing physiological blood pressure and wall shear stress to endothelial cells. Analyst 2021;146:5913-22. https://doi.org/10.1039/D1AN01049B.
• [39] Aboelkassem Y, Virag Z. A hybrid Windkessel-Womersley model for blood flow in arteries. J Theor Biol 2019;462:499-513. https://doi.org/10.1016/j.jtbi.2018.12.005.
• [40] Sato K, Sato K. Recent progress in the development of microfluidic vascular models. Anal Sci 2018;34:755-64. https://doi.org/10.2116/analsci.17R006.