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Adrenocortical tissue formed by transplantation of normal clones of bovine adrenocortical cells in scid mice replaces the essential functions of the animals' adrenal glands

Nature Medicine volume 3, pages 978–983 (1997)Cite this article

Abstract

Xenotransplanted adrenocortical tissue of clonal origin was formed in immunodeficient (scid) mice by using techniques of cell transplantation. The experiments reported here used a single clone of bovine adrenocortical cells, but 5 of 20 other randomly selected clones also formed tissue. Most adrenalectomized animals bearing transplanted cells survived indefinitely, demonstrating that the cells restored the animals' capacity to survive in the absence of sodium supplementation. Formation of well-vascularized tissue at the site of transplantation was associated with stable levels of cortisol in the blood, replacing the mouse glucocorticoid (corticosterone). Ultrastructurally, the cultured cells before transplantation had characteristics of rapidly growing cells, but tissue formed in vivo showed features associated with active steroidogenesis. These experiments show that an endocrine tissue can be derived from a single, normal somatic cell.

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References

  1. Langer, R. & Vacanti, J.P. Tissue engineering. Science 260, 920–926 (1993).

    Article  CAS  Google Scholar 

  2. Winn, S.R. et al. Polymer-encapsulated cells genetically modified to secrete human nerve growth factor promote the survival of axotomized septal cholinergic neurons. Proc. Notl. Acad. Sci. USA 91, 2324–2328 (1994).

    Article  CAS  Google Scholar 

  3. Vogt, P.M. et al. Genetically modified keratinocytes transplanted to wounds reconstitute the epidermis. Proc. Notl. Acad. Sci. USA 91, 9307–9311 (1994).

    Article  CAS  Google Scholar 

  4. Pavlath, G.K., Rando, T.A. & Blau, H.M. Transient immunosuppressive treatment leads to long-term retention of allogeneic myoblasts in hybrid myofibers. J. Cell Biol. 127, 1923–1932 (1994).

    Article  CAS  Google Scholar 

  5. Crane, G.M., Ishaug, S.L. & Mikos, A.G. Bone tissue engineering. Nature Med. 1, 1322–1324 (1995).

    Article  CAS  Google Scholar 

  6. Moullier, P., Bohl, D. Cardoso J., Heard, J. M. . & Danos, O. Long-term delivery of a lysosomal enzyme by genetically modified fibroblasts in dogs. Nature Med. 1, 353–357 (1995).

    Article  CAS  Google Scholar 

  7. Aebischer, P. et al. Intrathecal deliveiy of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nature Med. 2, 696–699 (1996).

    Article  CAS  Google Scholar 

  8. Lacorazza, H.D., Flax J.D., Snyder, E. Y. & Jendoubi M. Expression of human β-hexosaminidase α-subunit gene (the gene defect of Tay-Sachs disease) in mouse brains upon engraftment of transduced progenitor cells. Nature Med. 2, 424–429 (1996).

    Article  CAS  Google Scholar 

  9. Hornsby, P.J. & McAllister, J.M. Culturing steroidogenic cells, in: Methods in Enzymology. 206. (eds. Waterman, M. R. St Johnson, E. F.) 371–380 (Academic, San Diego, 1991).

    Google Scholar 

  10. Hornsby, P.J. et al. Changes in gene expression during senescence of adrenocortical cells in culture. J. Steroid Biochem. Mol. Biol. 43, 385–395 (1992).

    Article  Google Scholar 

  11. Hornsby, P.J. Culturing steroidogenic cells in: Cell and Tissue Culture: Laboratory Procedures, 17B (eds. Griffiths, J. B., Doyle, A. St Newell, D. G.) 7.1–7.9 (Wiley, Chichester, UK, 1994).

    Google Scholar 

  12. Hornsby, P.J., Aldern, K.A. & Harris, S.E. Clonal variation in response to adrenocorticotropin in cultured bovine adrenocortical cells: Relationship to senescence. J. Cell. Physiol. 129, 395–402 (1986).

    Article  CAS  Google Scholar 

  13. Hornsby, P.J. et al. Loss of expression of a differentiated function gene, steroid 17α-hydroxylase, as adrenocortical cells senesce in culture. Proc. Natl. Acad. Sci. USA 84, 1580–1584 (1987).

    Article  CAS  Google Scholar 

  14. Ryan, R.F., Hancock, J.P., McDonald, J. & Hornsby, P.J. Cellular senescence involves stochastic processes causing loss of expression of differentiated function genes: Visualization by in situ hybridization for steroid 17α-hydroxylase in bovine adrenocortical cells. Exp. Cell Res. 180, 36–48 (1989).

    Article  CAS  Google Scholar 

  15. Cheng, C.Y. & Hornsby, P.J. Expression of 11 β-hydroxylase and 21-hydroxylase in long-term cultures of bovine adrenocortical cells requires extra cellular matrix factors. Endocrinology 130, 2883–2889 (1992).

    Article  CAS  Google Scholar 

  16. Tait, J.F. & Tail, S.A.S. Recent perspectives on the history of the adrenal cortex. [The Sir Henry Dale lecture for 1979].J. Endocrlnol. 83, 3P–24P (1979).

    CAS  Google Scholar 

  17. Perkins, L.M. & Payne, A.H. Quantification of P450sccp P45017ap and iron sulfur protein reductase in Leydig cells and adrenals of inbred strains of mice. Endocrinology 123, 2675–2682 (1988).

    Article  CAS  Google Scholar 

  18. van Weerden W. M., Bierings H. G., van Steenbrugge G. J., de Jong F. H. & Schroder F. H. Adrenal glands of mouse and rat do not synthesize androgens. Life Sci. 50, 857–861 (1992).

    Article  CAS  Google Scholar 

  19. Keeney, D.S., Jenkins, C.M. & Waterman, M.R. Developmentally regulated expression of adrenal 17α-hydroxylase cytochrome P450 in the mouse embryo. Endocrinology 136, 4872–1879 (1995).

    Article  CAS  Google Scholar 

  20. Pauly, J.E. Morphological observations on the adrenal cortex of the laboratory rat. Endocrinology 60, 247–264 (1957).

    Article  CAS  Google Scholar 

  21. Neville, A.M. & O'Hare, M.J. The Human Adrenal Cortex: Pathology and Biology — An Integrated Approach. (Springer-Verlag, Berlin, 1982).

    Book  Google Scholar 

  22. Friend, D.S. & Gilula, N.B. A distinctive cell contact in the rat adrenal cortex. J. Cell Biol. 53, 148–163 (1972).

    Article  CAS  Google Scholar 

  23. Reaven, E., Spicher, M. . & Azhar S. Microvillar channels: A unique plasma membrane compartment for concentrating lipoproteins on the surface of rat adrenal cortical cells. J. Lipid Res. 30, 1551–1560 (1989).

    CAS  PubMed  Google Scholar 

  24. Plump, A.S. et al. Apolipoprotein A-I is required for cholesteryl ester accumulation in steroidogenic cells and for normal adrenal steroid production. J. Clin. Invest. 97 2660–2671 (1996).

    Article  CAS  Google Scholar 

  25. Idelman, S. The ultrastructure of the mammalian adrenal cortex. Int. Rev. Cytol. 27 181–281 (1970).

    Article  CAS  Google Scholar 

  26. Apkarian, R.P. & Curtis, J.C. Hormonal regulation of capillary fenestrae in the rat adrenal cortex: Quantitative studies using objective lens staging scanning electron microscopy. Scand. Electron Microsc. 1986, 1381–1393 (1986).

    Google Scholar 

  27. Hammond, K.D., Torrance, J.M. & DiDomenico, M. Glucocorticoid receptors in murine erythroleukaemic cells. J. Recept. Res. 7, 667–678 (1987).

    Article  CAS  Google Scholar 

  28. Bosma, M.J., Phillips, R.A. & Schuler, W. The scid Mouse: Characterization and Potential Uses. (Springer-Verlag, Berlin, 1989).

    Book  Google Scholar 

  29. Volpe, R. et al. New animal models for human autoimmune thyroid disease: Xenografts of human thyroid tissue in severe combined immunodeficient (SCID) and nude mice. Harm. Metab. Res. 25, 623–627 (1993).

    Article  CAS  Google Scholar 

  30. Martin, A. et al. Preservation of functioning human thyroid organoids in the scid mouse. 1. System characterization. J. Clin. Endocrinol. Metab. 77 305–310 (1993).

    CAS  PubMed  Google Scholar 

  31. Wright, N. & Alison, M. The Biology of Epithelial Cell Populations, 1. (Clarendon, Oxford, 1984).

    Google Scholar 

  32. Rotten, C.S. Stem Cells. (Academic Press, London, 1997).

    Google Scholar 

  33. Hornsby, P.J. The regulation of adrenocortical function by control of growth and structure. in: Adrenal Cortex.(eds Anderson, D. C. St Winter, J. S. D.) 1–31 (Butterworths, London, 1985).

    Google Scholar 

  34. Boudreau, N., Myers, C. & Bissell, M.J. From laminin to lamin: Regulation of tissue-specific gene expression by the ECM. Trends Cell Biol. 5, 1–4 (1995).

    Article  CAS  Google Scholar 

  35. Gumbiner, B.M. Cell adhesion: The molecular basis of tissue architecture and morphogenesis. Cell 84, 345–357 (1996).

    Article  CAS  Google Scholar 

  36. Li, C.H., Adrenocorticotropin 45. Revised amino acid sequences for sheep and bovine hormones. Biochem. Biophys. Res. Common. 49, 835–839 (1972).

    Article  CAS  Google Scholar 

  37. Uhler, M., Herbert, E., D'Eustachio, P. & Ruddle, F.D. The mouse genome contains two nonallelic pro-opiomelanocortin genes. J. Biol. Chem. 258, 9444–9453 (1983).

    CAS  PubMed  Google Scholar 

  38. Forough, R. et al. Differential transforming abilities of non-secreted and secreted forms of human fibroblast growth factor-1. J. Biol. Chem. 268, 2960–2968 (1993).

    CAS  PubMed  Google Scholar 

  39. Butcher, R.N., McCullough, K.C., Jarry, C. & Bryant, J., C-treated 3T3/B (3T3/A31) cell feeder layers in hybridoma technology. J. Immunol. Methods 107, 245–251 (1988).

    Article  CAS  Google Scholar 

  40. Luo, X., Ikeda, Y. & Parker, K.L. A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 77 481–490 (1994).

    Article  CAS  Google Scholar 

  41. Dunn, T.B. Normal and pathologic anatomy of the adrenal gland of the mouse, including neoplasms. J. Notl. Cancer Inst. 44, 1323–1389 (1970).

    CAS  Google Scholar 

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  1. Hufftngton Center on Aging and Department of Cell Biology, Baylor College of Medicine, Houston, Texas, 77030, USA

    Michael Thomas, S. Robert Northrup & Peter J. Hornsby

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Thomas, M., Northrup, S. & Hornsby, P. Adrenocortical tissue formed by transplantation of normal clones of bovine adrenocortical cells in scid mice replaces the essential functions of the animals' adrenal glands. Nat Med 3, 978–983 (1997). https://doi.org/10.1038/nm0997-978

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