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Design and Fabrication of a Three-Dimensional In Vitro System for Modeling Vascular Stenosis

Published online by Cambridge University Press:  17 July 2017

Rebecca S. Jones ,
Pin H. Chang ,
Tzlil Perahia ,
Katrina A. Harmon ,
Lorain Junor ,
Michael J. Yost ,
Daping Fan ,
John F. Eberth  and
Richard L. Goodwin
Rebecca S. Jones
Affiliation:
Biomedical Engineering Program, College of Engineering and Computing, University of South Carolina, Columbia, SC 29208, USA Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29209, USA
Pin H. Chang
Affiliation:
Biomedical Engineering Program, College of Engineering and Computing, University of South Carolina, Columbia, SC 29208, USA Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29209, USA
Tzlil Perahia
Affiliation:
Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29209, USA
Katrina A. Harmon
Affiliation:
Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29209, USA
Lorain Junor
Affiliation:
Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29209, USA
Michael J. Yost
Affiliation:
Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA
Daping Fan
Affiliation:
Biomedical Engineering Program, College of Engineering and Computing, University of South Carolina, Columbia, SC 29208, USA Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29209, USA
John F. Eberth
Affiliation:
Biomedical Engineering Program, College of Engineering and Computing, University of South Carolina, Columbia, SC 29208, USA Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29209, USA
Richard L. Goodwin*
Affiliation:
Department of Biomedical Sciences, School of Medicine, University of South Carolina, Greenville, SC 29605, USA
*
*Corresponding author. rlgoodwin@sc.edu
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Abstract

Vascular stenosis, the abnormal narrowing of blood vessels, arises from defective developmental processes or atherosclerosis-related adult pathologies. Stenosis triggers a series of adaptive cellular responses that induces adverse remodeling, which can progress to partial or complete vessel occlusion with numerous fatal outcomes. Despite its severity, the cellular interactions and biophysical cues that regulate this pathological progression are poorly understood. Here, we report the design and fabrication of a three-dimensional (3D) in vitro system to model vascular stenosis so that specific cellular interactions and responses to hemodynamic stimuli can be investigated. Tubular cellularized constructs (cytotubes) were produced, using a collagen casting system, to generate a stenotic arterial model. Fabrication methods were developed to create cytotubes containing co-cultured vascular cells, where cell viability, distribution, morphology, and contraction were examined. Fibroblasts, bone marrow primary cells, smooth muscle cells (SMCs), and endothelial cells (ECs) remained viable during culture and developed location- and time-dependent morphologies. We found cytotube contraction to depend on cellular composition, where SMC-EC co-cultures adopted intermediate contractile phenotypes between SMC- and EC-only cytotubes. Our fabrication approach and the resulting artery model can serve as an in vitro 3D culture system to investigate vascular pathogenesis and promote the tissue engineering field.

Keywords

collagenvascular stenosisbioreactorarterial modelin vitro culture
Type
Biological Science Applications
Information
Microscopy and Microanalysis , Volume 23 , Issue 4 , August 2017 , pp. 859 - 871
Copyright
© Microscopy Society of America 2017 

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Footnotes

†

Current address: Department of Civil and Environmental Engineering, College of Engineering, University of Michigan, Ann Arbor, MI 48109, USA.

‡

Current address: Department of Emergency Medicine, Crozer-Chester Medical Center, Upland, PA 19013, USA.

References

Achilli, M. & Mantovani, D. (2010). Tailoring mechanical properties of collagen-based scaffolds for vascular tissue engineering: The effects of pH, temperature and ionic strength on gelation. Polymers 2, 664–680.CrossRefGoogle Scholar
Azuma, K., Ichimura, K., Mita, T., Nakayama, S., Jin, W.L., Hirose, T., Fujitani, Y., Sumiyoshi, K., Shimada, K., Daida, H., Sakai, T., Mitsumata, M., Kawamori, R. & Watada, H. (2009). Presence of alpha-smooth muscle actin-positive endothelial cells in the luminal surface of adult aorta. Biochem Biophys Res Commun 380, 620–626.Google Scholar
Biechler, S.V., Junor, L., Evans, A.N., Eberth, J.F., Price, R.L., Potts, J.D., Yost, M.J. & Goodwin, R.L. (2014). The impact of flow-induced forces on the morphogenesis of the outflow tract. Front Physiol 5, 225.Google Scholar
Chiu, J.-J. & Chien, S. (2011). Effects of disturbed flow on vascular endothelium: Pathophysiological basis and clinical perspectives. Physiol Rev 91, 327–387.CrossRefGoogle ScholarPubMed
Devlin, A.M., Clark, J.S., Reid, J.L. & Dominiczak, A.F. (2000). DNA synthesis and apoptosis in smooth muscle cells from a model of genetic hypertension. Hypertension 36, 110–115.Google Scholar
Eberth, J.F., Gresham, V.C., Reddy, A.K., Popovic, N., Wilson, E. & Humphrey, J.D. (2009). Importance of pulsatility in hypertensive carotid artery growth and remodeling. J Hypertens 27, 2010–2021.Google Scholar
Eberth, J.F., Popovic, N., Gresham, V.C., Wilson, E. & Humphrey, J.D. (2010). Time course of carotid artery growth and remodeling in response to altered pulsatility. Am J Physiol Heart Circ Physiol 299, H1875–H1883.Google Scholar
Evans, H.J., Sweet, J.K., Price, R.L., Yost, M. & Goodwin, R.L. (2003). Novel 3D culture system for study of cardiac myocyte development. Am J Physiol Heart Circ Physiol 285, H570–H578.CrossRefGoogle ScholarPubMed
Galis, Z.S. & Khatri, J.J. (2002). Matrix metalloproteinases in vascular remodeling and atherogenesis: The good, the bad, and the ugly. Circ Res 90, 251–262.Google Scholar
Hahn, C. & Schwartz, M.A. (2009). Mechanotransduction in vascular physiology and atherogenesis. Nat Rev Mol Cell Biol 10, 53–62.Google Scholar
Heusch, G., Libby, P., Gersh, B., Yellon, D., Böhm, M., Lopaschuk, G. & Opie, L. (2014). Cardiovascular remodelling in coronary artery disease and heart failure. Lancet 383, 1933–1943.Google Scholar
Hirai, J., Kanda, K., Oka, T. & Matsuda, T. (1994). Highly oriented, tubular hybrid vascular tissue for a low pressure circulatory system. ASAIO J 40, M383–M388.Google Scholar
Ingber, D.E. (1997). Tensegrity: The architectural basis of cellular mechanotransduction. Annu Rev Physiol 59, 575–599.Google Scholar
Kakisis, J.D., Liapis, C.D., Breuer, C. & Sumpio, B.E. (2005). Artificial blood vessel: The Holy Grail of peripheral vascular surgery. J Vasc Surg 41, 349–354.Google Scholar
Kanda, K. & Matsuda, T. (1994). In vitro reconstruction of hybrid arterial media with molecular and cellular orientations. Cell Trans 3, 537–545.Google Scholar
Kanda, K., Matsuda, T. & Oka, T. (1993). In vitro reconstruction of hybrid vascular tissue. Hierarchic and oriented cell layers. ASAIO J 39, M561–M565.Google ScholarPubMed
Kwak, B.R., Bäck, M., Bochaton-Piallat, M.-L., Caligiuri, G., Daemen, M.J.A.P., Davies, P.F., Hoefer, I.E., Holvoet, P., Jo, H., Krams, R., Lehoux, S., Monaco, C., Steffens, S., Virmani, R., Weber, C., Wentzel, J.J. & Evans, P.C. (2014). Biomechanical factors in atherosclerosis: Mechanisms and clinical implications. Eur Heart J 35, 3013–3020.CrossRefGoogle ScholarPubMed
L’Heureux, N., Germain, L., Labbé, R. & Auger, F.A. (1993). In vitro construction of a human blood vessel from cultured vascular cells: A morphologic study. J Vasc Surg 17, 499–509.Google Scholar
L’Heureux, N., Pâquet, S., Labbé, R., Germain, L. & Auger, F.A. (1998). A completely biological tissue-engineered human blood vessel. FASEB J 12, 47–56.Google Scholar
Li, D.Y., Toland, A.E., Boak, B.B., Atkinson, D.L., Ensing, G.J., Morris, C.A. & Keating, M.T. (1997). Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis. Hum Mol Genet 6, 1021–1028.Google Scholar
Libby, P. & Hansson, G.K. (2015). Inflammation and immunity in diseases of the arterial tree: Players and layers. Circ Res 116, 307–311.Google Scholar
Libby, P., Ridker, P.M. & Hansson, G.K. (2011). Progress and challenges in translating the biology of atherosclerosis. Nature 473, 317–325.Google Scholar
Mammoto, T., Mammoto, A. & Ingber, D.E. (2013). Mechanobiology and developmental control. Annu Rev Cell Dev Biol 29, 27–61.Google Scholar
McElhinney, D.B., Parry, A.J., Reddy, V.M., Hanley, F.L. & Stanger, P. (1998). Left pulmonary artery kinking caused by outflow tract dilatation after transannular patch repair of tetralogy of Fallot. Ann Thorac Surg 65, 1120–1126.Google Scholar
Ng, C.P. & Swartz, M.A. (2003). Fibroblast alignment under interstitial fluid flow using a novel 3-D tissue culture model. Am J Physiol Heart Circ Physiol 284, H1771–H1777.Google Scholar
Niklason, L.E., Gao, J., Abbott, W.M., Hirschi, K.K., Houser, S., Marini, R. & Langer, R. (1999). Functional arteries grown in vitro. Science 284, 489–493.CrossRefGoogle ScholarPubMed
Shi, Z.-D., Ji, X.-Y., Qazi, H. & Tarbell, J.M. (2009). Interstitial flow promotes vascular fibroblast, myofibroblast, and smooth muscle cell motility in 3-D collagen I via upregulation of MMP-1. Am J Physiol Heart Circ Physiol 297, H1225–H1234.CrossRefGoogle ScholarPubMed
Shi, Z.-D. & Tarbell, J.M. (2011). Fluid flow mechanotransduction in vascular smooth muscle cells and fibroblasts. Ann Biomed Eng 39, 1608–1619.Google Scholar
Sung, K.E., Su, G., Pehlke, C., Trier, S.M., Eliceiri, K.W., Keely, P.J., Friedl, A. & Beebe, D.J. (2009). Control of 3-dimensional collagen matrix polymerization for reproducible human mammary fibroblast cell culture in microfluidic devices. Biomaterials 30, 4833–4841.CrossRefGoogle ScholarPubMed
Tan, H., Biechler, S., Junor, L., Yost, M.J., Dean, D., Li, J., Potts, J.D. & Goodwin, R.L. (2013). Fluid flow forces and rhoA regulate fibrous development of the atrioventricular valves. Dev Biol 374, 345–356.Google Scholar
Thiriet, M., Delfour, M. & Garon, A. (2015). Vascular stenosis: An introduction. In PanVascular Medicine, Lanzer, P. (Ed.), pp. 781–868. Berlin, Heidelberg: Springer.Google Scholar
Valarmathi, M.T., Davis, J.M., Yost, M.J., Goodwin, R.L. & Potts, J.D. (2009). A three-dimensional model of vasculogenesis. Biomaterials 30, 1098–1112.Google Scholar
Valarmathi, M.T., Goodwin, R.L., Fuseler, J.W., Davis, J.M., Yost, M.J. & Potts, J.D. (2010). A 3-D cardiac muscle construct for exploring adult marrow stem cell based myocardial regeneration. Biomaterials 31, 3185–3200.Google Scholar
van Meeteren, L.A. & ten Dijke, P. (2012). Regulation of endothelial cell plasticity by TGF-β. Cell Tissue Res 347, 177–186.Google Scholar
Weinberg, C.B. & Bell, E. (1986). A blood vessel model constructed from collagen and cultured vascular cells. Science 231, 397–400.CrossRefGoogle ScholarPubMed
Williams, J.C.P., Barratt-Boyes, B.G. & Lowe, J.B. (1961). Supravalvular aortic stenosis. Circulation 24, 1311–1318.Google Scholar
Yost, M.J., Baicu, C.F., Stonerock, C.E., Goodwin, R.L., Price, R.L., Davis, J.M., Evans, H., Watson, P.D., Gore, C.M., Sweet, J., Creech, L., Zile, M.R. & Terracio, L. (2004). A novel tubular scaffold for cardiovascular tissue engineering. Tissue Eng 10, 273–284.Google Scholar