Abstract
Regeneration of functioning tissue essentially involves recapitulating relevant aspects of organogenesis, so that the starting composite of cells, matrix, and molecular factors develops into the desired structure and physiology. A crucial aspect of development is local cell—cell communication; that is, molecular regulatory factors are more typically paracrine and autocrine than endocrine in nature. Autocrine loops were originally thought of predominantly as being involved in pathological behavior, but it is becoming increasingly clear that a large portion of normal physiological behavior—and a tremendous portion of development—is strongly regulated by autocrine factors (1). Thus, continuing progress of the field of tissue engineering will require increased understanding of how autocrine loops operate, so that they can be designed or manipulated systematically. We have made an effort in this direction, and some early experimental and modeling results can be found in the literature (2–5). In this chapter, we describe the methods we have used for creating autocrine cell loops and quantitatively assessing their operation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Sporn, M. B. and Roberts, A. B. (1992) Autocrine secretion—10 years later. Ann. Intern. Med. 117, 408–414.
Forsten, K. and Lauffenburger, D. A. (1992a) Autocrine ligand binding to cell receptors: mathematical analysis of competition by solution “decoys.” Biophys. J. 61, 518–529.
Forsten, K. and Lauffenburger, D. A. (1992b) interrupting autocrine ligand-receptor binding: comparison between receptor blockers and ligand decoys. Biophys. J. 63, 857–861.
Lauffenburger, D. A., Chu, L., French, A., Oehrtman, G., Reddy, C., Wells, A., Niyogi, S., and Wiley, H. S. (1996) Engineering dynamics of growth factors and other therapeutic ligands. Biotechnol. Bioeng. 52, 61–80.
Will, B. H., Lauffenburger, D. A., and Wiley, H. S. (1995) studies on engineered autocrine systems: requirements for ligand release from cells producing an artificial growth factor. Tissue Eng. 1, 81–94.
McConnell, H. M., Owicki, J. C., Parce, J. W., Miller, D. L., Baxter, G. T., Wada, H. G., Pitchford, S. (1992) the cytosensor microphysiometer: biological applications of silicon technology. Science 257, 1906–1912.
Hirst, M. A., Pitchford, S. (1993) use of a single assay system to assess functional coupling of a variety of receptors. J. NIH. Res. 5, 69.
Gossen, M. and Bujard, H. (1992) tight control of gene expression in mammalian cells by tetracycline-responsive promoters. PNAS 89, 5547–5551.
Derynck, R., Roberts, A. B., Winkler, M. E., Chen, E. Y. and Goeddel, D. V. (1984) Human transforming growth factor-a: precursor structure and expression in E.coli. Cell 38, 287–297.
Chen, W. S., Lazar, C. S., Poenie, M., Tsien, R. Y., Gill, G. N., and Rosenfeld, M. G. (1987) requirement for intrinsic protein tyrosine kinase in the immediate and late actions of the EGF receptor. Nature 328, 820–823.
Kriegler, M. (1990) Gene transfer and expression (Kriegler, M., ed.), H. Freeman, New York, pp. 96–98.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Oehrtman, G., Walker, L., Will, B., Opresko, L., Wiley, H.S., Lauffenburger, D.A. (1999). Quantitative Assessment of Autocrine Cell Loops. In: Morgan, J.R., Yarmush, M.L. (eds) Tissue Engineering Methods and Protocols. Methods in Molecular Medicine™, vol 18. Humana Press. https://doi.org/10.1385/0-89603-516-6:143
Download citation
DOI: https://doi.org/10.1385/0-89603-516-6:143
Publisher Name: Humana Press
Print ISBN: 978-0-89603-516-4
Online ISBN: 978-1-59259-602-7
eBook Packages: Springer Protocols