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Endothelial Cell-Selective Materials for Tissue Engineering in the Vascular Graft Via a New Receptor

Bio/Technology volume 9, pages 568–572 (1991)Cite this article

Abstract

We have found a novel adhesion receptor on the human endothelial cell for the peptide sequence Arg-Glu-Asp-Val (REDV), which is present in the III-CS domain of human plasma fibronectin, with a dissociation constant of 2.2 × 10−6 M and 5.8 × 106 sites/cell. When a synthetic peptide containing this sequence was immobilized on otherwise cell nonadhesive substrates, endothelial cells attached and spread but fibroblasts, vascular smooth muscle cells, and platelets did not. Endothelial mono-layers on REDV were nonthrombogenic: endothelial cells attached and spread upon other receptor-binding domains of fibronectin and laminin, but with lesser degrees of specificity or with a loss of nonthrombogenicity. This approach may provide a basis for a tissue engineered vascular graft where endothelial cell attachment is desired, but not the attachment of other blood vessel wall cells and blood platelets.

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References

  1. Yeager, A. and Callow, A.D. 1988. New graft materials and current approaches to an acceptable small diameter vascular graft. Trans. Am. Soc. Artif. Intern. Organs 34: 88–94.

    Article  CAS  Google Scholar 

  2. Andrade, J.D. and Hlady, V. 1986. Protein adsorption and materials biocompatibility: a tutorial review and suggested hypotheses. Adv. Polymer Sci. 79: 1–63.

    Article  CAS  Google Scholar 

  3. Park, K., Mao, F.W. and Park, H. 1990. Morphological characterization of surface-induced platelet activation. Biomaterials 11: 24–31.

    Article  CAS  Google Scholar 

  4. Bennett, J.S., Shatil, S.J., Power, J.W. and Gartner, T.K. 1988. Interaction of fibrinogen with its platelet receptor: differential effects of alpha and gamma chain fibrinogen peptides on the glycoprotein complex. J. Biol. Chem. 263: 12948–12953.

    CAS  PubMed  Google Scholar 

  5. Hawiger, J., Kloczewiak, M., Bednarek, M.A. and Timmons, S. 1989. Platelet receptor recognition domains on the alpha chain of human fibrinogen: structure and analysis. Biochemistry 28: 2909–2919.

    Article  CAS  Google Scholar 

  6. Timmons, S., Bednarek, M.A., Kloczewiak, M. and Hawiger, J. 1989. Antiplatelet hybrid peptides analogous to receptor recognition domains on gamma and alpha chains of human fibrinogen. Biochemistry 28: 2919–2923.

    Article  CAS  Google Scholar 

  7. Girma, J.-P., Meyer, D., Verweij, C.L., Pannekoek, H. and Sixma, J.J. 1987. Structure-function relationship of human von Willebrand factor. Blood 70: 605–611.

    CAS  PubMed  Google Scholar 

  8. Horbett, T.A., Schway, M.B. and Ratner, B.D. 1985. Hydrophilic-hydrophobic copolymers as cell substrates: effect on 3T3 cell growth rates. J. Colloid Interface Sci. 104: 28–39.

    Article  CAS  Google Scholar 

  9. Horbett, T.A. and Schway, M.B. 1988. Correlations between mouse 3T3 cell spreading and serum fibronectin adsorption on glass and hydroxyethylmethacrylate-ethylmethacrylate copolymers. J. Biomed. Mater. Res. 22: 763–793.

    Article  CAS  Google Scholar 

  10. Chinn, J.A., Horbett, T.A., Ratner, B.D., Schway, M.B., Haque, Y. and Hauschka, S.D. 1989. Enhancement of serum fibronectin adsorption and the clonal plating efficiencies of Swiss mouse 3T3 fibroblast and MM 14 mouse myoblast cells on polymer substrates modified by radiofrequency plasma deposition. J. Colloid Interface Sci. 127: 67–87.

    Article  CAS  Google Scholar 

  11. Dejana, E., Colello, S., Conforti, G., Abbadini, M., Gaboli, M. and Marchisio, P.C. 1988. Fibronectin and vitronectin regulate the organization of their respective Arg-Gly-Asp adhesion receptors in cultured human endothelial cells. J. Cell Biol. 107: 1215–1223.

    Article  CAS  Google Scholar 

  12. Dejana, E., Colella, S., Languino, L.R., Balconi, G., Corbascio, G.C., Marchisio, P. C. 1987. Fibrinogen induces adhesion, spreading and microfilamenl organization of human endothelial cells in vitro. J. Cell Biol. 104: 1403–1411.

    Article  CAS  Google Scholar 

  13. Massia, S.P. and Hubbell, J.A. 1990. Covalently attached GRGD on polymer surfaces promotes biospecific adhesion of mammalian cells. Ann. N.Y. Acad. Sci. 589: 261–270.

    Article  CAS  Google Scholar 

  14. Massia, S.P. and Hubbell, J.A. 1990. Covalent surface immobilization of Arg-Gly-Asp- and Tyr-Ile-Gly-Ser-Arg-containing peptides to obtain well-defined cell-adhesive substrates. Anal. Biochem. 187: 292–301.

    Article  CAS  Google Scholar 

  15. Massia, S.P. and Hubbell, J.A. 1991. Human endothelial cell interactions with surface-coupled adhesion peptides on a nonadhesive glass substrate and two polymeric biomaterials. J. Biomed. Mater. Res. 25: 223–242.

    Article  CAS  Google Scholar 

  16. Cheresh, D.A. 1987. Human endothelial cells synthesize and express an Arg-Gly-Asp directed adhesion receptor involved in attachment to fibrinogen and von Willebrand factor. Proc. Natl. Acad. Sci. USA 84: 6471–6475.

    Article  CAS  Google Scholar 

  17. Dejana, E., Languino, L.R., Colella, S., Corbascio, G.C., Plow, E., Ginsberg, M. and Marchisio, P.C. 1988. The localization of a platelet gpIIb-IIIa-related protein in endothelial cell adhesion structures. Blood 71: 566–572.

    CAS  PubMed  Google Scholar 

  18. Charo, I.F., Bekeart, L.S. and Phillips, D.R. 1987. Platelet glycopro-tein Ilb-IIIa-like proteins mediate endothelial cell attachment to adhesive proteins and the extracellular matrix. J. Biol. Chem. 262: 9935–9938.

    CAS  PubMed  Google Scholar 

  19. Yannariello-Brown, J., Wewer, U., Liotta, L. and Madri, J.A. 1988. Distribution of a 69-kD laminin-binding protein in aortic and micro-vascular endothelial cells: modulation during cell attachment, spreading, and migration. J. Cell Biol. 106: 1773–1786.

    Article  CAS  Google Scholar 

  20. Graf, J., Iwamoto, Y., Sasaki, M., Martin, G.R., Kleinman, H.K., Robey, F.A. and Yamada, Y. 1987. Identification of an amino acid sequence in laminin mediating cell altachment, chcmotaxis, and receptor binding. Cell 48: 989–996.

    Article  CAS  Google Scholar 

  21. Kleinman, H.K., Graf, J., Iwamoto, Y., Sasaki, M., Schasteen, C.S., Yamada, Y., Martin, G.R. and Robey, F.A. 1989. Identification of a second active site in laminin for promotion of cell adhesion and migration and inhibition of in vivo melanoma lung colonization. Arch. Biochem. Biophys. 272: 39–45.

    Article  CAS  Google Scholar 

  22. Humphries, M.J., Akiyama, S.K., Komoriya, A., Olden, K. and Yamada, K.M. 1986. Identification of an alternatively spliced site in human plasma fibronectin that mediates cell type specific adhesion. J. Cell Biol. 103: 2637–2647.

    Article  CAS  Google Scholar 

  23. Massia, S.P. and Hubbell, J.A. 1991. An RGD spacing of 440 nm is sufficient for fibroblast spreading and 140 nm for focal contact and stress fiber formation. In revision.

    Google Scholar 

  24. Izzard, C.S. and Lochner, L.R. 1976. Cell-to-substrate contacts in living fibroblasts: an interference reflexion study with an evaluation of the technique. J. Cell Sci. 21: 129–159.

    CAS  PubMed  Google Scholar 

  25. Scatchard, G. 1949. The attractions of proteins for small molecules and ions. Ann. N.Y. Acad. Sci. 51: 660–672.

    Article  CAS  Google Scholar 

  26. McGonigle, P. and Molinoff, P.B. 1989. Quantitative aspects of drug-receptor interactions, p. 183–201. In: Basic Neurochemistry, 4th edition. Siegel, G.J., Agranoff, B. W., Albers, R. W., and Molinoff, P. B. (Eds.). Raven Press, New York.

    Google Scholar 

  27. Pytela, R., Pierschbacher, M.D., Ginsberg, M.H., Plow, E.F. and Ruoslahti, E. 1986. Platelet membrane glycoprotein Ilb-IIIa member of a family of arginine-glycine-aspartic-acid specific adhesion receptors. Science 231: 1559–1561.

    Article  CAS  Google Scholar 

  28. Beer, J.H. and Coller, B.S. 1989. Immobilized RGD-containing peptides as molecular probes of platelet gpIIb/IIIa receptors. Thromb. Haemostas. 62: 341 (abst).

    Google Scholar 

  29. Jaffe, E.A., Nachman, R.L. and Becker, C.E. 1973. Culture of human endothelial cells derived from umbilical cord veins. J. Clin. Invest. 52: 2745–2757.

    Article  CAS  Google Scholar 

  30. Desai, N.P. and Hubbell, J.A. 1991. A solution technique to incorporate polyethylene oxide and other water soluble polymers into surfaces of polymeric biomaterials. Biomaterials In press.

    Google Scholar 

  31. Akiyama, S.K. and Yamada, K.M. 1985. The interaction of plasma fibronectin with fibroblastic cells in suspension. J. Biol. Chem. 260: 4492–4500.

    CAS  PubMed  Google Scholar 

  32. Hubbell, J.A. and McIntire, L.V. 1986. Technique for visualization and analysis of mural thrombogenesis. Rev. Sci. Instrum. 57: 893–897.

    Article  Google Scholar 

  33. Desai, N.P. and Hubbell, J.A. 1989. The short-term blood biocom-patibility of poly(hydroxyethyl methacrylate-co-methyl methacrylate) in an in vitro flow system measured by digital videomicroscopy. J. Biomater. Sci. Polymer Edn. 1: 123–146.

    Article  CAS  Google Scholar 

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Author notes

  1. Jeffrey A. Hubbell: Corresponding author.

Authors and Affiliations

  1. Department of Chemical Engineering, University of Texas, Austin, Texas, 78712-1062

    Jeffrey A. Hubbell, Stephen P. Massia, Neil P. Desai & Paul D. Drumheller

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  1. Jeffrey A. Hubbell
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Hubbell, J., Massia, S., Desai, N. et al. Endothelial Cell-Selective Materials for Tissue Engineering in the Vascular Graft Via a New Receptor. Nat Biotechnol 9, 568–572 (1991). https://doi.org/10.1038/nbt0691-568

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