Summary
For the past 60 years, fundamental discoveries in eukaryotic biology using mammalian cell cultures have been significant but modest relative to the enormous potential. Combined with advances in technologies of cell and molecular biology, mammalian cell culture technology is becoming a major, if not essential tool, for fundamental discovery in eukaryotic biology. Reconstruction of the milieu for cells has progressed from simple salt solutions supporting brief survival of tissues outside the body to synthesis of the complete set of structurally defined nutrients, hormones and elements of the extracellular matrix needed to reconstruct complex tissues from cells. The isolation of specific cell types in completely defined environments reveals the true complexity of the mammalian cell and its environment as a dynamic interactive physiological unit. Cell cultures provide the tool for detection and dissection of the mechanism of action of cellular regulators and the genes that determine individual aspects of cell behavior. The technology underpins advances in virology, somatic cell genetics, endocrinology, carcinogenesis, toxicology, pharmacology, hematopoiesis and immunology, and is becoming a major tool in develomental biology, complex tissue physiology and production of unique mammalian cell-derived biologicals in industry.
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Schleiden, E. J. Beitrage zur phytogenesis. Arch. Anat. Physiol. Wiss. Med. (J. Muller), 1838:137–176; 1838.
Schwann, T.Mikroskopische Untersuchungen uber die Ubereinstimmung in der Struktur und dem Wachsthum der Tiere und Pflanzen. Ostwalds Klassiker der Exakten Wissenschaften. Berlin, Verlag der Sander schen Buchhandlung 176∶1910; 1839.
Bernard, C.Le, cons sur les phenomenes de la vie, communs aux animaux et aux vegetaux. (2 Vols.). Paris, Bailliere; 1878–79.
Burrows, M. T. The cultivation of tissues of the chick embryo outside the body. J. Am. Med. 55:2057–2058; 1910.
Carrel, A. On the permanent life of tissues outside of the organism. J. Exp. Med. 15:516–528; 1912.
Carrel, A. Tissue culture and cell physiology. Physiol. Rev. 4:1–20; 1924.
Gey, G. O.; Thalheimer, W. Observation of the effects of insulin introduced into the medium of tissue culture. J. Am. Med. Assoc. 82:1609; 1924.
Gey, G. O. An improved technique for massive culture. Am. J. Cancer 17:752–756; 1933.
Gey, G. O.; Gey, M. C. The maintenance of human normal cells and tumor cells in continuous culture. Am. J. Cancer 27:45–76; 1936.
Gey, G. O.; Seegar, G. E.; Hellman, L. M. The production of a gonadotropic substance (prolan) by placental cells in culture. Science 88:306–307; 1938.
Gey, G. O.; Coffman, W. D.; Kubicek, M. T. Tissue culture studies of the proliferative capacity of cervical carcinoma and normal epithelium. Cancer Res. 12:264–265; 1952.
Ehrmann, R. L.; Gey, G. O. The growth of cells on a transparent gel of reconsitituted rat tail collagen. J. Natl. Cancer Inst. 16:1375–1415; 1956.
Earle, W. R. Production of malignancy in vitro. IV. The mouse fibroblast cultures and changes seen in living cells. J. Natl. Cancer Inst. 4:165–212; 1943.
Hayflick, L.; Moorhead, P. S. The serial cultivation of human diploid strains. Exp. Cell Res. 25:585–621; 1961.
Todaro, G. J.; Green, H. Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J. Cell Biol. 17:299–313; 1963.
Perry, R. P. The cellular sites of synthesis of ribosomal and 4S RNA. Proc. Natl. Acad. Sci. USA 48:2179–2186; 1962.
Scherrer, K.; Darnell, J. E. Sedimentation characteristics of rapidly labelled RNA from HeLa cells. Biochem. Biophys. Res. Commun. 7:486–490; 1962.
Penman, S.; Sherrer, K.; Becker, Y., et al. Polyribosomes in normal and poliovirus-infected HeLa cells and their relationship to messenger-RNA. Proc. Natl. Acad. Sci. USA 49:654–662; 1963.
Steiner, D. F.; Oyer, P. E. The biosynthesis of insulin and a probable precursor of insulin by a human islet adenoma. Proc. Natl. Acad. Sci. 57:473–480; 1967.
Steiner, D. F.; Clark, J. L.; Nolan, C., et al. Proinsulin and the biosynthesis of insulin. Recent Prog. Horm. Res. 25:207–282; 1969.
Reich, E.; Franklin, R. M.; Shatkin, A. J., et al. Effect of actinomycin D on cellular nucleic acid synthesis and virus production. Science 134:556–557; 1961.
Hsu, T. C. Mammalian chromosomes in vitro. J. Hered. 43:167–172; 1952.
Tjio, J. H.; Levan, A. The chromosome number of man. Separat ur Herediatas 42:1–6; 1956.
Huberman, J. A.; Riggs, A. D. On the mechanism of DNA replication in mammalian chromosomes. J. Mol. Biol. 32:327–341; 1968.
Caspersson, T.; Hulten, M.; Lindsten, J., et al. Identification of different Robertsonian translocations in man by quinarcine mustard fluorescence analysis. Hereditas 67:213–220; 1971.
Wang, H. C.; Fedoroff, S. Banding in human chromosomes treated with trypsin. Nature New Biol. 235:52–54; 1972.
Frye, L. D.; Edidin, M. The rapid intermixing of cell surface antigens after formation of mouse-human heterokaryons. J. Cell. Sci. 7:319–335; 1970.
Temin, H. M.; Rubin, H. Characteristics of an assay for Rous Sarcoma virus and Rous Sarcoma cells in tissue culture. Virology 6:669–688; 1958.
Dulbecco, R. Viral carinogenesis. Cancer Res. 21:975–980; 1961.
Stoker, M.; MacPherson, I. Studies on transformation of hamster cells by polyoma virus in vitro. Virology 14:359–370; 1961.
Sato, G. The role of serum in cell culture. In: Litwak, G., ed.Biochemical Acions of Hormones, Vol. 3, Academic Press, NY; 1975:391–396.
Barnes, D.; Sirbasku, D., eds.,Peptide Growth Factors, Methods Enzymol., Vols. 146, 147. Academic Press, NY; 1987.
Metcalf, D.; Moore, M. A. S., eds,Hematopoietic Cells, North-Holland. Amsterdam (1971).
Clark, S. C.; Kamen, R. The human hematopoietic colony-stimulating factors. Science 236:1229–1237; 1987.
Pestka, S., ed. Interferons.Methods Enzymol. 79; 1981.
Sabato, G. D.; Langone, J. J.; Van Vunakis, H., eds. Immunochemical techniques.tMethods Enzymol. 116H; 1985.
Clemens, M. J.; Morris, A. G.; Gearing, A. J. H., eds.Lymphokines and Interferons, IRL Press. Oxford; 1987.
Webb, D. R.; Pierce, C. W.; Cohen, S., eds.Molecular Basis of Lymphokine Action, Humana Press, NY; 1988.
Hayashi, I.; Sato, G. Replacement of serum by hormones permits growth of cells in a defined medium. Nature 259:132–134; 1976.
Barnes, D.; Sato, G. Serum-free culture: a unifying approach. Cell 22:649–655; 1980.
Barnes, D. W.; McKeehan, W. L.; Sato, G. H. Cellular endocrinology: integrated physiology in vitro. In Vitro Cell. Devel. Biol. 23:659–662; 1987.
Bottenstein, J.; Hayashi, I.; Hutchings, S. The growth of cells in serum-free hormone-supplemented media. Methods Enzymol. 58:94–109; 1979.
Sato, G.; Ross, R., eds.Hormones and Cell Culture, Cold Spring Harbor, NY; 1979.
Sato, G. H.; Pardee, A. B.; Sirbasku, D. A., eds.Growth of Cells in Hormonally Defined Media, Cold Spring Harbor, NY; 1982.
Barnes, D. W.; Sirbasku, D. A.; Sato, G. H., eds.Cell Culture Methods for Cell Biology, Vols. 1–4, Alan R. Liss, NY; 1984.
Mather, J., eds.Mammalian Cell Culture: The Use of Serum-Free Hormone-Supplemented Media, Plenum Press, NY; 1984.
Bottenstein, J. E.; Sato, G., eds.Cell Culture in the Neurosciences, Vol. 1–3, Plenum Press, NY; 1985.
Taub, M., ed.Tissue Culture of Epithelial Cells, Plenum Press, NY; 1985.
Varmus, H. Retroviruses. Science 240:1427–1435; 1988.
Kohler, G.; Milstein, C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497; 1975.
Tonegawa, S. Nobel Lecture in physiology or medicine-1987. Somatic generation of immune diversity. In Vitro Cell. Devel. Biol. 24:253–265; 1988.
Hunter, T.; Cooper, J. A. Protein-tyrosine kinases. Annu. Rev. Biochem. 54:897–930; 1985.
Bishop, J. M. Oncogenes. Sci. Am. 246:80–82; 1982.
Weinberg, R. A. The action of oncogenes in the cytoplasm and nucleus. Science 230:770–776; 1985.
Hunter, T. Oncogenes and proto-oncogenes: how do they differ? J. Natl. Cancer Inst. 73:773–786; 1984.
McKeehan, W. L.; Adams, P. S.; Rosser, M. P. Direct mitogenic effects of insulin, epidermal growth factor, glucocorticoid, cholera toxin, unknown pituitary factors and possibly prolactin, but not androgen, on normal rat prostate epithelial cells in serum-free, primary cell culture. Cancer Res. 44:1998–2010; 1984.
McKeehan, W. L.; Adams, P. S. Assay of growth factors for prostate epithelial cells. J. Tissue Culture Methods 10:151–154; 1986.
Crabb, J. W.; Armes, L. G.; Carr, S. A., et al. Complete primary structure of prostatropin, a prostate epithelial cell growth factor. Biochemistry 25:4988–4993; 1986.
McKeehan, W. L.; Adams, P. S.; Fast, D. Different hormonal requirements for androgen-independent growth of normal and tumor epithelial cells from rat prostate. In Vitro Cell. Devel. Biol. 23:147–152; 1987.
Ham, R. G.; McKeehan, W. L. Media and growth requirements. Methods Enzymol. 58:44–93; 1979.
Ham, R. G. Survival and growth requirements of non-transformed cells. Handbook Exptl. Pharmacol. 57:13–88; 1981.
McKeehan, W. L.; McKeehan, K. A. Extracellular regulation of fibroblast multiplication: a direct kinetic approach to analysis of role of low molecular weight nutrients and serum growth factors. J. Supramol. Struct. Cell. Biochem. 15:83–110; 1981.
Bettgar, W. J.; Ham, R. G. The nutrient requirements of cultured mammalian cells. Adv. Nutr. Res. 4:249–286; 1982.
Reid, L.; Jefferson, D. Cell culture studies using extracts of extracellular matrix to study growth and differentiation in mammalian cells. In: Mather, J., ed.Mammalian Cell Culture, Plenum Press, NY; 1984:239–280.
Reid, L. M.; Abren, S. L.; Montgomery, K. Extracellular matrix and hormonal regulation of synthesis and abundance of messenger RNAs in cultured liver cells. In: Arias, L. M.; Jakoby, W. B.; Popper, H., et al., eds.The Liver: Biology and Pathobiology, Raven Press; 1988∶717–737.
Reid, L. M. Generic methods for defined hormonal and matrix conditions for studies of growth of gene expression in differentiated epithelial. In: Pollard, J. W.; Walker, J. M., eds.Methods in Molecular Biology, Vol. 5, Humana Press, Inc., in press, 1989.
Sporn, M. B.; Todaro, G. J. Autocrine secretion and malignant transformation of cells. N. Engl. J. Med. 303:878–880; 1980.
Ross, R.; Raines, E. W.; Bowen-Pope; D. F. The biology of platelet-derived growth factor. Cell 46:155–169; 1986.
Deuel, T. F. Polypeptide growth factors: roles in normal and abnormal cell growth. Annu. Rev. Cell Biol. 3:443–492; 1987.
Stampfer, M. R. Cholera toxin stimulation of human mammary epithelial cells in culture. In Vitro 18:531–537; 1982.
Rheinwald, J. G.; Green, H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell 6:331–343; 1975.
Clayton, D. F.; Darnell, J. E., Jr. Changes in liver-specific compared to common gene transcription during primary culture of mouse hepatocytes. Mol. Cell. Biol. 3:1552–1561; 1983.
Jefferson, D. M.; Clayton, D. F.; Darnell, J. E., Jr., et al. Postranscriptional modulation of gene expression in cultured rat hepatocytes. Mol. Cell. Biol. 4:1929–1934; 1984.
Sporn, M. B.; Roberts, A. B.; Wakefield, L. M., et al. Transforming growth factor-beta: biological function and chemical structure. Science 233:532–534; 1986.
Roberts, A. B.; Sporn, M. B. Transforming growth factor beta. Adv. Cancer Res. 51:107–145; 1988.
Kan, M.; DiSorbo, D.; Hou, J., et al. High and low affinity binding of heparin-binding growth factor to a 130-kDa receptor correlates with stimulation and inhibition of growth of a differentiated human hepatoma cell. J. Biol. Chem. 263:11306–11313; 1988.
Hoshi, H.; Kan, M.; Chen, J. K., et al. Comparative endocrinology-paracrinology-autocrinology of human adult large vessel endothelial and smooth muscle cells. In Vitro Cell. Devel. Biol. 24:309–320; 1988.
Kan, M.; Huang, J.; Mansson, P.-E., et al. Heparin-binding growth factor type one (acidic fibroblast growth factor): a potential biphasic autocrine and paracrine regulator of hepatocyte regeneration. Proc. Natl. Acad. Sci. USA 86:7432–7436; 1989.
Puck, T. T., ed.The Mammalian Cell as a Microorganism, Holden-Day, Inc., San Francisco; 1975.
Fischer, A. Die bedeutung der aminosauren fur die gewelezellen in vitro. Acta. Physiol. Scand. 2:145–148; 1941.
White, P. R. Cultivation of animal tissues in vitro in nutrients of precisely known constitution. Growth 10:231–239; 1946.
Morgan, J. F.; Morton, H. J.; Parker, R. C. Nutrition of animal cells in tissue culture. Proc. Soc. Exp. Biol. Med. 73:1–8; 1950.
Morton, H. J.; Pasieka, A. E.; Morgan, J. F. The nutrition of animal cells cultivated in vitro. J. Biophys. Biochem. Cytol. 2:589–596; 1956.
Waymouth, C. A serum-free nutrient solution sustaining rapid and continuous proliferation of strain L (Earle) mouse cells. J. Natl. Cancer Inst. 17:315–325; 1956.
Evans, V. J.; Bryant, J. C. McQuilkin, W. T., et al. Studies of nutrient media for tissue cells in vitro. Cancer Res. 16:87–94; 1956.
Moore, G. E.; Gerner, R. E.; Franklin, H. A. Culture of normal human leukocytes. J. Am. Med. Assoc. 199:519–524; 1967.
Eagle, H. Nutrition needs of mammalian cells in tissue culture. Science 122:501–504; 1955.
Eagle, H.; Piez, K. The population-dependent requirement by cultured mammalian cells for metabolites which they can synthesize. J. Exp. Med. 116:29–43; 1962.
McKeehan, W. L.; Hamilton, W. G.; Ham, R. G. Selenium is an essential nutrient for growth of WI-38 diploid human fibroblasts. Proc. Natl. Acad. Sci. USA 73:2023–2027; 1976.
Kano-Sueoka, T.; Cohen, D. M.; Yamaizumi, Z., et al. Phosphoethanolamine as a growth factor of a mammary carcinoma cell line of rat. Proc. Natl. Acad Sci. USA 76:5741–5744; 1979.
Bettger, W. J.; Boyce, S. T.; Walthall, B. J., et al. Rapid clonal growth and serial passage of human diploid fibroblasts in a lipid-enriched synthetic medium supplemented with epidermal growth factor, insulin, and dexamethasone. Proc. Natl. Acad. Sci. USA 78:5588–5592; 1981.
Tsao, M. C.; Walthall, B. J.; Ham, R.G. Clonal growth of normal human epidermal keratinocytes in a defined medium J. Cell. Physiol. 110:219–229; 1982.
Hammond, S. L.; Ham, R. G.; Stampfer, M. R. Serum-free growth of human mammary epithelial cells: rapid clonal growth in defined medium and extended serial passage with pituitary extract. Proc. Natl. Acad. Sci. USA. 81:5435–5439; 1984.
Bettger, W. J.; McKeehan, W. L. Mechanisms of cellular nutrition. Physiol. Rev. 66:1–35; 1986.
McKeehan, W. L.; McKeehan, K. A. Epidermal growth factor modulates extracellular Ca2+ requirement for multiplication of normal human skin fibroblasts. Exp. Cell Res. 123:397–400; 1979.
McKeehan, W. L.; McKeehan, K. A. Serum factors modulate the cellular requirements of Ca2+, K+, Mg2+, phosphate ions, and 2-oxocarboxylic acids for multiplication of normal human fibroblasts. Proc. Natl. Acad. Sci. USA 77:3417–3421; 1980.
Newsholme, E. A.; Crabtree, B.; Ardawi, M. S. The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells. Biosci. Rep. 5:393–400; 1985.
McKeehan, W. L. Glutaminolysis in animal cells. In: Morgan, M. J., ed.Carbohydrate Metabolism in Cultured Cells, Plenum, London, 1986:111–150.
McKeehan, W. L.; McKeehan, K. A.; Calkins, D. Extracellular regulation of fibroblast multiplication. Quantitative differences in nutrient and serum factor requirements for multiplication of normal and SV40-virus transformed human lung cells. J. Biol. Chem. 256:2973–2981; 1981.
Salmon, W.; Daughaday, W. A hormonally-controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J. Lab. Clin Med. 49:825–836; 1957.
Clemmons, D. R.; Van Wyk, J. J. Somatomedin: physiological control and effects on cell proliferation. In: Baserga, R., ed.Tissue Growth Factors, Handbook of Experimental Pharmacology. Springer-Verlag, New York, Vol. 57, 1981:161–208.
Froesch, E. R.; Schmid, C.; Schwander, J., et al. Actions of insulin-like growth factors. Annu. Rev. Physiol. 47:443–467; 1985.
Sirbasku, D. A. Estrogen induction of growth factors specific for hormone-responsive mammary, pituitary, and kidney tumor cells. Proc. Natl. Acad. Sci. USA 75:3786–3790; 1978.
James, R.; Bradshaw, R. A. Polypeptide growth factors. Annu. Rev. Biochem. 53:259–292; 1984.
Burgess, W. H.; Maciag, T. The heparin-binding (fibroblast) growth factor family of proteins Annu. Rev. Biochem. 58:575–606; 1989.
Rifkin, D. B.; Moscatelli, D. Recent developments in the cell biology of basic fibroblast growth factor. J. Cell Biol. 109:1–6; 1989.
Rosenberg, R. D.; Lam, L. Correlation between structure and function of heparin. Proc. Natl. Acad. Sci. USA 76:1218–1222; 1979.
Fedarko, N. S.; Conrad, H. E., A unique heparan sulfate in the nuclei of hepatocytes: structural changes with the growth state of the cells. J. Cell Biol. 102:587–599; 1986.
Li, M. L.; Aggeler, J.; Farson, D. A., et al. Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells. Proc. Natl. Acad. Sci. USA 84:136–140; 1987.
Vlodavsky, I.; Folkman, J.; Sullivan, R., et al. Endothelial cellderived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix. Proc. Natl. Acad. Sci. USA 84:2292–2296; 1987.
Spray, D. C.; Fujita, M.; Saez, J. C., et al. Proteoglycans and glycosaminoglycans induce gap junction synthesis and function in primary liver cultures. J Cell Biol 105:541–551; 1987.
Rojkind, M.; Gatmaitan, Z.; Mackensen, S., et al. Connective tissue biomatrix: its isolation and utilization for long-term cultures of normal rat hepatocytes. J. Cell. Biol. 87:255–263; 1980.
Muschel, R.; Khoury, G.; Reid, L. M. Regulation of insulin mRNA abundance and adenylation: dependence on hormones and matrix substrata. Mol. Cell. Biol. 6:337–341; 1986.
Kleinman, H. K.; Luckenbill-Edds, L.; Cannon, F. W., et al. Use of extracellular matrix components for cell culture. Anal. Biochem. 166:1–13; 1987.
Ailenberg, M.; Tung, P. S.; Pelletier, M., et al. Modulation of Sertoli cell functions in the two-chamber assembly by peritubular cells and extracellular matrix. Endocrinology 122:2604–2612; 1988.
Hynes, R. O. Integrins: a family of cell surface receptors. Cell 48:549–554; 1987.
Ruoslahti, E.; Pierschbacher, M. D. New perspectives in cell adhesion: RGD and integrins. Science 238:491–497; 1987.
Ignotz, R. A.; Endo, T.; Massague, J. Regulation of fibronectin and type I collagen mRNA levels by transforming growth factor-beta. J. Biol. Chem. 262:6443–6446; 1987.
Chen, J. K.; Hoshi, H.; McKeehan, W. L. Transforming growth factor type beta specifically stimulates synthesis of proteoglycan in human adult arterial smooth muscle cells. Proc. Natl. Acad. Sci. USA 84:5287–5291; 1987.
Ignotz, R. A.; Massague, J. Cell adhesion protein receptors as targets for transforming growth factor-beta action. Cell 51:189–197; 1987.
Rizzino, A. Transforming growth factor-beta: multiple effects on cell differentiation and extracellular matrices. Devel. Biol. 130:411–422; 1988.
Puck, T. T.; Marcus, P. I. A rapid method for viable cell titration and clone production with HeLa cells in tissue culture. Proc. Natl. Acad. Sci. USA 41:432–437; 1955.
Puck, T. T.; Marcus, P. I.; Cieciura, S. J. Clonal growth of mammalian cells in vitro. J. Exp. Med. 103:273–283; 1956.
Ham, R. G.; Puck, T. T. Quantitative colonial growth of isolated mammalian cells. Methods Enzymol. 5:90–119; 1962.
Kao, F. T.; Puck, T. T. Genetics of somatic mammalian cells, VII. Induction and isolation of nutritional mutants, in Chinese hamster cells. Proc. Natl. Acad. Sci. USA 60:1275–1281; 1968.
Thompson, L. H.; Mankovitz, R.; Baker, R. M., et al. Isolation of temperature-sensitive mutants of L-cells. Proc. Natl. Acad. Sci. USA 66:377–384; 1970.
Choi, K. W.; Bloom, A. D. Cloning human lymphocytes in vitro. Nature 227:171–173; 1970.
Konigsberg, I. R. Clonal analysis of myogenesis. Science 140:1273–1284; 1963.
Coon, H. G. Clonal stability and phenotypic expression of chick cartilage cells in vitro. Proc. Natl. Acad. Sci. USA 55:66–73; 1966.
Coon, H. G.; Cahn, R. D. Differentiation, in vitro: effects of Sephadex fractions of chick embryo extract. Science 153:1116–1119; 1966.
Cahn, R. D.; Cahn, M. B. Heritability of cellular, differentiation: clonal growth and expression of differentiation in retinal pigment cells in vitro. Proc. Natl. Acad. Sci. USA 55:106–114; 1966.
Ham, R. G. Cloning of mammalian cells. Met. Cell. Physiol. 5:37–74; 1972.
Sanford, K. K.; Earle, W. R.; Likely, G. D. The growth in vitro of single isolated cells. J. Natl. Cancer Inst. 9:229–246; 1948.
Harrison, R. G. Observations, on the living developing nerve fiber. Proc. Soc. Exp. Biol. Med. 4:140–143; 1907.
Harrison, R. G. The outgrowth of the nerve fiber as a mode of protoplasmic movement. J. Exp. Zool. 9:787–848; 1910.
Sato, G.; Zaroff, L.; Mills, S. E. Tissue culture populations and their relation to the tissue of origin. Proc. Natl. Acad. Sci. USA 46:963–972; 1960.
Schindler, R.; Day, M.; Fischer, G. A. Culture of neoplastic mast cells and their synthesis of 5-hydroxy-tryptamine and histamine in vitro. Cancer Res. 19:47–51; 1959.
Thompson, E. B.; Tomkins, G. M.; Curran, J. F. Induction of tyrosine alpha-ketoglutarate transaminase by steroid hormones in a newly established tissue culture cell line. Proc. Natl. Acad. Sci. USA 56:296–303; 1966.
Yaffe, D. Retention of differentiation potentialities during prolonged cultivation of myogenic cells. Proc. Natl. Acad. Sci. USA 61:477–483; 1968.
Leighton, J.; Estes, L. W.; Mansukhani, S., et al. A cell line derived from normal dog kidney (MDCK) exhibiting, qualities of papillary adenocarcinoma and of renal tubular epithelium. Cancer 26:1022–1028; 1970.
Knowles, B. B.; Howe, C. C.; Aden, D. P. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science 209:497–499; 1980.
Buonassisi, V.; Sato, G.; Cohen, A. I. Hormone-producing cultures of adrenal and pituitary tumor origin. Proc. Natl. Acad. Sci. USA 48:1184–1190; 1962.
Yasamura, Y.; Tashjian, A. H., Jr.; Sato, G. H. Establishment of four functional, clonal strains of animal cells in culture. Science 154:1186–1189; 1966.
Mohit, B.; Sato, G. H. Improved in vitro survival of normal, functional spleen cells. Science 157:449–451; 1967.
Augusti-Tocco, G.; Sato, G. Establishment of functional clonal, lines of neurons from mouse neuroblastoma. Proc. Natl. Acad. Sci. USA 64:311–315; 1969.
Sato, G.; Augusti-Tocco, G.; Posner, M. Hormone-secreting and hormone-responsive cell cultures. Recent Prog. Horm. Res. 26:539–546; 1970.
Rosenthal, M. D.; Wishnow R. M.; Sato, G. H. In vitro growth and differentiation of clonal populations of multipotential mouse cells derived from a transplantable testicular teratocarcinoma. J. Natl. Cancer Inst. 44:1001–1014; 1970.
Sato, G., ed.Functionally Differentiated Cell Lines. Alan R. Liss, NY; 1981.
Hammond, S. L.; Ham, R. G.; Stampfer, M. R. Serum-free growth of human mammary epithelial cells: rapid clonal growth in defined medium and extended serial passage with pituitary extract. Proc. Natl. Acad. Sci. USA 81:5435–5439; 1984.
Sanford, K. K.; Likely, G. D.; Earle, W. R. The development of variations in transplantability and morphology within a clone of mouse fibroblasts transformed to sarcoma-producing cells in vitro. J. Natl. Cancer Inst. 15:215–230; 1954.
Abercrombie, M.; Heaysman, J. E. M. Observations on the social behavior of cells in tissue culture. Exp. Cell Res. 6:293–306; 1954.
Stoker, M.; MacPherson, I. Studies on transformation of hamster cells by polyoma virus in vitro. Virology 14:359–370; 1961.
Todaro, G. J.; Green, H. Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J. Cell Biol. 17:299–313; 1963.
MacPherson, I.; Montagnier, L. Agar suspension culture for the selective assay of cells transformed by polyoma virus. Virology 23:291–294; 1964.
Holley, R. W.; Kiernan, J. A. “Contact inhibition” of cell division in 3T3 cells. Proc. Natl. Acad. Sci. USA 60:300–304; 1964.
Aaronson, S. A.; Todaro, G. J. Basis for the acquisition of malignant potential by mouse cells cultivated in vitro. Science 162:1024–1026; 1968.
Pollack, R. E.; Green, H.; Todaro, G. J. Growth control in cultured cells: selection of sublines with increased sensitivity to contact inhibition and decreased tumor-producing ability. Proc. Natl. Acad. Sci. USA 60:126–133; 1968.
Dulbecco, R. Topoinhibition and serum requirement of transformed and untransformed cells. Nature 227:802–806; 1970.
Freedman, V. H.; Shin, S. L. Cellular tumorigenicity in nude mice: correlation with cell growth in semi-solid medium. Cell 3:355–359; 1974.
Doolittle, R. F.; Hunkapiller, M. W.; Hood, L. E., et al. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221:275–277; 1983.
Waterfield, M. D.; Scrace, G. T.; Whittle, N., et al. Plateletderived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature 304:35–39; 1983.
Downward, J.; Yarden, Y.; Mayes, E., et al., Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 307:521–527; 1984.
Sherr, C. J.; Rettenmier, C. W.; Sacca, R., et al. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell 41:665–676; 1985.
Stiles, C. D. The molecular biology of platelet-derived growth factor. Cell 33:653–655; 1983.
Rollins, B. J.; Stiles, C. D. Regulation of c-myc and c-fos protooncogene expression by animal cell growth factors. In Vitro Cell. Devel. Biol. 24:81–84; 1988.
De Larco, J. E.; Todaro, G. J. Growth factors from murine sarcoma virus-transformed cells. Proc. Natl. Acad. Sci. USA 75:4001–4005; 1978.
Derynck, R. Transforming growth factor-alpha: structure and biological activities. J. Cell. Biochem. 32:293–304; 1986.
Cochran, B. H.; Zumstein, P.; Zullo, J., et al. Differentiation colony hybridization: molecular cloning from a zero data base. Methods Enzymol. 147:64–85; 1987.
Scher, C. D.; Pledger, W. J. Identification of platelet-derived growth factor-modulated proteins. Methods Enzymol. 147:85–92; 1987.
Okada, Y. The fusion of Ehrlich’s tumor cells caused by HVJ virus in vitro. Biken J. 1:103–110; 1958.
Harris, H. Behaviour of differentiated nuclei in heterokaryons of animal cells from different species. Nature 206:583–588; 1965.
Pontecorvo, G. Production of mammalian somatic cell hybrids by means of polyethylene glycol treatment. Somatic Cell Genet. 1:397–400; 1975.
Ruddle, F. H. A new era in mammalian gene mapping: somatic cell genetics and recombinant DNA methodologies. Nature 294:115–120; 1981.
Shows, T. B.; Sakaguchi, A. Y.; Naylor, S. L. Mapping the human genome, cloned genes, DNA polymorphisms, and inherited disease. Adv. Hum. Genet. 12:341–452; 1982.
Ege, T.; Ringertz, N. R. Viability of cells reconstituted by virus-induced fusion of minicells with anucleate cells. Exp. Cell Res. 94:469–473; 1975.
Fournier, R. E.; Ruddle, F. H. Microcell-mediated transfer of murine chromosomes into mouse, Chinese hamster, and human somatic cells. Proc. Natl. Acad. Sci. USA 74:319–323; 1977.
Tunnacliffe, A.; Goodfellow, P. Attached cell antigen 28.3.7 mapping to human chromosome 15 characterizes TPA-induced differentiation of the promyelocytic HL-60 cell line to give macrophage/monocyte populations. EMBO J. 2:2007–2012; 1983.
Saxon, P. J.; Srivatsan, E. S.; Leipzig, G. V., et al. Selective transfer of individual human chromosomes to recipient cells. Mol. Cell. Biol. 5:140–146; 1985.
Sager, R. Genetic suppression of tumor formation. Adv. Cancer Res. 44:43–68; 1985.
Harris, H. The genetic analysis of malignancy. J. Cell Sci. Suppl. 4:431–444; 1986.
Stanbridge, E. J. Genetic regulation of tumorigenic expression in somatic cell hybrids, Klein, G., ed. Advances in Viral Oncology, Vol. 6, Raven Press, New York; 1987:83–102.
Stanbridge, E. J. Suppression of malignancy in human cells. Nature 260:17–20; 1976.
Klinger, H. P.; Suppression of tumorigenicity. Cytogenet. Cell Genet. 32:68–84; 1982.
Stanbridge, E. J. A case for human tumor-suppressor genes. Bioassays 3:252–255; 1985.
Klein, G. The approaching era of the tumor suppressor genes. Science 238:1539–1545; 1987.
Weissman, B. E.; Saxon, P. J.; Pasquale, S. R., et al. Introduction of a normal human chromosome 11 into a Wilms’ tumor cell line controls its tumorigenic expression. Scinece 236:175–180; 1987.
Stanbridge, E. J. A genetic basis for tumour suppression. In: Brock, G.; Marsh, J., eds. CIBA Found. Symp. No. 142. John Wiley and Sons, New York, 1989:149–159.
Davidson, R. L., ed.Somatic Cell Hybridization, Raven Press, New York; 1974.
Weiss, M. C.; Sparkes, R. S.; Bertolotti, R. Expression of differentiated functions in hepatoma cell hybrids: IX extinction and reexpression of liver-specific enzymes in rat hepatoma-Chinese hamster fibroblast hybrids. Somatic Cell Genet. 1:27–40; 1975.
Chin, A. C.; Fournier, R. E. A genetic analysis of extinction: trans-regulation of 16 liver-specific genes in hepatoma-fibroblast hybrid cells. Proc. Natl. Acad. Sci. USA 84:1614–1618; 1987.
Blau, H. M.; Chiu, C. P.; Webster, C. Cytoplasmic activation of human nuclear genes in stable heterocaryons. Cell 32:1171–1180; 1983.
Hardeman, E. C.; Chiu, C. P.; Minty, A., et al. The pattern of actin expression in human fibroblast x mouse muscle heterokaryons suggests that human muscle regulatory factors are produced. Cell 47:123–130; 1986.
Chin, A. C.; Fournier, R. E. Tissue-specific expresion of hepatic functions. Genetics aspects. Ann. N.Y. Acad. Sci. 478:120–130; 1986.
Stoscheck, C. M.; Carpenter, G. Biology of the A-431 cell: a useful organism for hormone research. J. Cell. Biochem. 23:191–202; 1983.
Cohen, S. Epidermal growth factor. Nobel Lecture in Physiology or Medicine-1986. In Vitro Cell. Devel. Biol. 23:239–246; 1987.
Carpenter, G. Receptors for epidermal growth factor and other polypeptide mitogens. Annu. Rev. Biochem. 56:881–914; 1987.
Yarden, Y.; Ulrich, A. Molecular analysis of signal transduction by growth factors. Biochemistry 27:3113–3119; 1988.
Chao, M. V.; Bothwell, M. A.; Ross, A. H., et al. Gene transfer and molecular cloning of the human NGF receptor. Science 232:518–521; 1986.
Robb, R. J.; Greene, W. C.; Rusk, C. M. Low and high affinity cellular receptors for interleukin 2. J. Exp. Med. 160:1126–1146; 1984.
Yarden, Y.; Escobedo, J. A.; Kuang, W. J., et al. Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors. Nature 323:226–232; 1986.
Dulak, N. C.; Temin, H. M. Multiplication-stimulating activity for chicken embryo fibroblasts from rat liver cell conditioned medium: a family of small polypeptides. J. Cell Physiol. 81:161–170; 1973.
Dulak, N. C.; Temin, H. M. A partially purified polypeptide fraction from rat liver cell conditioned medium with multiplication-stimulating activity for embryo fibroblasts. J. Cell Physiol. 81:153–160; 1973.
Greenstein, L. A.; Gaynes, L. A.; Romanus, J. A., et al. Purification of rat insulin-like growth factor II. Methods Enzymol. 146:259–269; 1987.
Mroczkowski, B.; Reich, M.; Chen, K., et al. Recombinant human epidermal growth factor precursor is a glycosylated membrane protein with biological activity. Mol. Cell. Biol. 9:2771–2778; 1989.
Wong, S. T.; Winchell, L. F.; McCune, B. K., et al. The TGF-alpha precursor expressed on the cell surface binds to the EGF receptor on adjacent cells, leading to signal transduction. Cell 56:495–506; 1989.
Kawasaki, E. S.; Ladner, M. B.; Wang, A. M., et al. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science 230:291–296; 1985.
Derynck, R.; Jarrett, J. A.; Chen, E. Y., et al. Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature 316:701–705; 1985.
Lawrence, D. A.; Pircher, R.; Jullien, P. Conversion of a high molecular weight latent beta-TGF from chicken embryo fibroblasts into a low molecular weight active beta-TGF under acidic conditions. Biochem. Biophys. Res. Commun. 133:1026–1034; 1985.
Orlidge, A.; D’Amore, P. A. Inhibition of capillary endothelial cell growth by pericytes and smooth muscle cells. J. Cell Biol. 105:1455–1462; 1987.
Lyons, R. M.; Keski-Oja, J.; Moses, H. L. Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium. J. Cell Biol. 106:1659–1665; 1988.
March, C. J.; Mosley, B.; Larsen, A., et al. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature 315:641–647; 1985.
Radeke, M. J.; Misko, T. P.; Hsu, C., et al. Gene transfer and molecular cloning of the rat nerve growth factor receptor. Nature 325:593–597; 1987.
Sims, J. E.; March, C. J.; Cosman, D., et al. cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily. Science 241:585–589; 1988.
Yamasaki, K.; Taga, T.; Hirata, Y., et al. Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor. Science 241:825–828; 1988.
Leung, D. W.; Spencer, S. A.; Cachianes, G., et al. Growth hormone receptor and serum binding protein: purification, cloning and expression. Nature 330:537–543; 1987.
Boutin, J. M.; Jolicoeur, C.; Okamura, H., et al. Cloning and expression of the rat prolactin receptor, a member of the growth hormone/prolactin receptor gene family. Cell 53:69–77; 1988.
Schimke, R. T. Gene amplification in cultured animal cells. Cell 37:705–713; 1984.
Gottesman, M. M.; Pastan, I. The multidrug transporter, a double-edged sword. J. Biol. Chem. 263:12163–12166; 1988.
Mishra, N.; Dunkel, M.; Mehlman, eds.Mammalian Cell Transformation by Chemical Carcinogens. Senate Press, Inc., Princeton Junction, NJ; 1980.
Ames, B. N.; Durston, W. E.; Yamasaki, E., et al. Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc. Natl. Acad. Sci. USA 70:2281–2285; 1973.
International Conference on Practical In Vitro Toxicology, Food and Chemical Toxicology 24 (6–7):447–818; 1986.
Tennant, R. W.; Margolin, B. H.; Shelby, M. D., et al. Prediction of chemical carcinogenicity in rodents from in vitro genetic toxicity assays. Science 236:933–941; 1987.
Balls, M. 4th International Workshop on In Vitro Toxicology. Crieff, Perthshire, Scotland, September 8–12, 1986. Xenobiotica 18(6):615–616; 1988.
Goldberg, A. M.; Frazier, J. M. Alternatives to animals in toxicity testing. Scientific American 261:24–30; 1989.
Nishizuka, Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature 334:661–665; 1988.
Weinstein, I. B. Effects of phorbol esters in cell culture and their relevance to short-term assays for tumor promoters. In: Mishra, N.; Dunkel, V.; Mehlman, M., eds.Mammalian Cell Transformation by Chemical Carcinogens, Vol. 1, Senate Press, Princeton Junction, NJ; 1980:427–446.
Michaell, R. H., Drummond, A. H.; Downes, C. P., eds.Inositol Lipids in Cell Signalling, Academic Press, NY; 1989.
Hedrick, S. M.; Cohen, D. I.; Nielsen, E. A., et al. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature 308:149–153; 1984.
Yanagi, Y.; Yoshikai, Y.; Leggett, K., et al. A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature 308:145–149;1984.
Stevens, L. C. Experimental production of testicular teratomas in mice. Proc. Natl. Acad. Sci. USA 52:654–661; 1964.
Pierce, G. B. Teratocarcinoma: model for a developmental concept of cancer. Curr. Top. Dev. Biol. 2:223–246; 1967.
Nicolas, J. F.; Jakob, H.; Jacob, F. Teratocarcinoma-derived cell lines and their use in the study of differentiation. In: Sato, G., ed.Functionally Differentiated Cell Lines. Alan R. Liss, NY; 1981:185–210.
Evans, M. J.; Kaufman, M. H. Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156; 1981.
Martin, G. R. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl. Acad. Sci. USA 78: 7634–7638; 1981.
Brinster, R. L. The effect of cells transferred into the mouse blastocyst on subsequent development. J. Exp. Med. 140:1049–1056; 1974.
Palmiter, R. D.; Brinster, R. L.; Hammer, R. E., et al. Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature 300:611–615; 1982.
Mansour, S. L.; Thomas, K. R.; Capecchi, M. R. Disruption of the proto-oncogene int-2 mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature 336:348–352; 1988.
Weinstein, R.; Stemerman, M. B.; Maciag, T. Hormonal requirements for growth of arterial smooth muscle cells in vitro: an endocrine approach to atherosclerosis. Science 212:818–820; 1981.
Maciag, T.; Kadish, J.; Wilkins, L., et al. Organizational behavior of human umbilical vein endothelial cells. J. Cell. Biol. 94:511–520; 1982.
Winkles, J. A.; Friesel, R.; Burgess, W. H., et al. Human vascular smooth muscle cells both express and respond to heparin-binding growth factor I (endothelial cell growth factor). Proc. Natl. Acad. Sci. USA 84:7124–7128; 1987.
Moscatelli, D.; Rifkin, D. B. Membrane and matrix localization of proteinases: a common theme in tumor cell invasion and angiogenesis. Biochim. Biophys. Acta 948:67–85; 1988.
Saksela, O.; Rifkin, D. B. Cell-associated plasminogen activation: regulation physiological functions. Annu. Rev. Cell. Biol. 4:93–126; 1988.
Walker, L. N.; Bowen-Pope, D. F.; Ross, R., et al. Production of platelet-derived growth factor-like molecules by cultured arterial smooth muscle cells accompanies proliferation after arterial injury. Proc. Natl. Acad. Sci. USA 83:7311–7315; 1986.
Sejersen, T.; Betsholtz, C.; Sjolund, M., et al. Rat skeletal myoblasts and arterial smooth muscle cells express the gene for the A chain but not the gene for the B chain (c-sis) of platelet-derived gerowth factor (PDGF) and produce a PDGF-like protein. Proc. Natl. Acad. Sci. USA 83:6844–6848; 1986.
Barrett, T. B.; Benditt, E. P. Sis (platelet-derived growth factor B chain) gene transcript levels are elevated in human atherosclerotic lesions compared to normal artery. Proc. Natl. Acad. Sci. USA 84:1099–1103; 1987.
Heldin, C. H.; Westermark, B.; Wasteson, A. Specific receptors for platelet-derived growth factor on cells derived from connective tissue and glia. Proc. Natl. Acad. Sci. USA 78:3664–3668; 1981.
Mansson, P. E.; Malark, M.; Sawada, H., et al. Heparin-binding (fibroblast) growth factors type one and two genes are co-expressed in proliferating normal human vascular endothelial and smooth muscle cells. In Vitro Cell. Devel. Biol., in press; 1990.
Raines, E. W.; Dower, S. K.; Ross, R. Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA. Science 243:393–396; 1989.
Sawada, H.; Kan, M.; McKeehan, W. L. Differential modulation of proliferation and heparin-binding (fibroblast) growth factor binding to human aortic endothelial cells and smooth muscle cells by interleukin-1 and tumor necrosis factor. In Vitro Cell. Devel. Biol., in press; 1990.
Lobb, R. R. Thrombin inactivates acidic fibroblast growth factor but not basic fibroblast growth factor. Biochemistry 27:2572–2578; 1988.
Grisham, J. W. A morphologic study of deoxyribonucleic acid synthesis and cell proliferation in regenerating rat liver; autoradiography with thymidine-H3. Cancer Res. 22:842–849; 1962.
Bucher, N. L. R.; Malt, R. A., eds.Regeneration of Liver and Kidney, Little Brown, Boston; 1971.
Friedman, J. M.; Chung, E. Y.; Darnell, J. E., Jr. Gene expression during liver regeneration. J. Mol. Biol. 179:37–53; 1984.
Baumann, H. Hepatic acute phase reaction in vivo and in vitro. In Vitro Cell. Devel. Biol. 25:115–126; 1989.
Marceau, N.; Blouin, M. J.; Germain, L., et al. Role of different epithelial cell types in liver ontogenesis, regeneration and neoplasia. In Vitro Cell. Devel. Biol. 25:336–341; 1989.
Fausto, N.; Mead, J. E. Regulation of liver growth: protooncogenes and transforming growth factors. Lab Invest. 60:4–13; 1989.
Wolff, J. A.; Yee, J. K.; Skelly, H. F., et al. Expression of retrovirally transduced genes in primary cultures of adult rat hepatocytes. Proc. Natl. Acad. Sci. USA 84:3344–3348; 1987.
Ledley, F. D.; Darlington, G. J.; Hahn, T., et al. Retroviral gene transfer into primary hepatocytes. Implications for genetic therpay of liver-specific functions. Proc. Natl. Acad. Sci. USA 84:5335–5339; 1987.
Wilson, J. M.; Johnston, D. E.; Jefferson, D. M., et al. Correction of the genetic defect in hepatocytes from the Watanabe heritable hyperlipidemic rabbit. Proc. Natl. Acad. Sci. USA 85:4421–4425; 1988.
Thompson, J. A.; Anderson, K. D.; DiPietro, J. M., et al. Sitedirected neovessel formation in vivo. Science 241:1349–1352; 1988.
Bell, E.; Sher, S.; Hull, B., et al. The reconstitution of living skin. J. Invest. Dermatol. 81 (1 Suppl):2s-10s; 1983.
Gallico, G. G.; O’Connor, N. E.; Compton, C. C., et al. Permanent coverage of large burn wounds with autologous cultured human epithelium. N. Engl. J. Med. 311:448–451; 1984.
Bell, E.; Moore, H.; Mitchie, C., et al. Reconstruction of a thyroid gland equivalent from cells and matrix materials. J. Exp. Zool. 232:277–285; 1984.
Weinberg, C. B.; Bell, E. A blood vessel model constructed from collagen and cultured vascular cells. Science 231:397–400; 1986.
Morgan, J. R.; Barrandon, Y.; Green, H., et al. Expression of an exogenous growth hormone gene by transplantable human epidermal cells. Science 237:1476–1479; 1987.
Zwiebel, J. A.; Freeman, S. M.; Kantoff, P. W., et al. High-level recombinant gene expression in rabbit endothelial cells transduced by retroviral vectors. Science 243:220–222; 1988.
Wilson, J. M.; Birinyi, L. K.; Saloman, R. N., et al. Implantation of vascular grafts lined with genetically modified endothelial cells. Science 244:1344–1346; 1989.
Thompson, J. A.; Handenschild, C. C.; Anderson, K. D., et al. Induction of organoid neovascular structures in vivo. Proc. Natl. Acad. Sci., in press; 1989.
Thilly, B., ed.,Mammalian Cell Technology, Butterworths & Co., London; 1986.
Griffiths, J. B.; Spear, R., eds.Modern Approaches to Animal Cell Technology, Butterworths & Co., London; 1987.
James, K.; Bell, G. T. Human manoclonal antibody production. J. Immunol. Methods 100:5–40; 1987.
Murakami, H. Serum-free media used for cultivation of hybridomas. In: Mizrahi, A., ed.Monoclonal Antibodies: Production and Application, Alan R. Liss, NY, 1989:107–113.
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This article is the first of a series of invited reviews aimed at identifying fundamental contributions and current challenges associated with research activities in subdiscriplines of cell and developmental biology in vitro. This treatise is dedicated to Dr. Brian Kimes, Program Director at the National Cancer Institute, whose vision, encouragement and support have contributed significantly to modern developments in mammalian cell culture.
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Keehan, W.L.M., Barnes, D., Reid, L. et al. Frontiers in mammalian cells culture. In Vitro Cell Dev Biol 26, 9–23 (1990). https://doi.org/10.1007/BF02624149
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DOI: https://doi.org/10.1007/BF02624149