Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Review
  • Published:

Prospects for the use of nuclear transfer in human transplantation

Nature Biotechnology volume 17, pages 1171–1174 (1999)Cite this article

Abstract

The successful application of nuclear transfer techniques to a range of mammalian species has brought the possibility of human therapeutic cloning significantly closer. The objective of therapeutic cloning is to produce pluripotent stem cells that carry the nuclear genome of the patient and then induce them to differentiate into replacement cells, such as cardiomyocytes to replace damaged heart tissue or insulin-producing β cells for patients with diabetes. Although cloning would eliminate the critical problem of immune incompatibility, there is also the task of reconstituting the cells into more complex tissues and organs in vitro. In the review, we discuss recent progress that has been made in this field as well as the inherent dangers and scientific challenges that remain before these techniques can be used to harness genetically matched cells and tissues for human transplantation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Procedure for human therapeutic cloning.
Figure 2: The ability of NT to reset the life span of senescent somatic cells6.

Similar content being viewed by others

References

  1. Lanza, R.P. & Chick, W.L. Yearbook of cell and tissue transplantation 1996/1997. (Kluwer, Dordrecht, The Netherlands; 1996 ).

    Book  Google Scholar 

  2. Briggs, R. & King, T.J. Transplantation of living cell nuclei from blastula cells into enucleated frog's eggs. Proc. Natl. Acad. Sci. USA 38, 455–463 ( 1952).

    Article  CAS  Google Scholar 

  3. McKinnell, R.G. Intraspecific nuclear transplantation in frogs. J. Hered. 53, 199–207 (1962).

    Article  CAS  Google Scholar 

  4. McGrath, J. & Solter, D. Nuclear transplantation in mouse embryos by microsurgery and cell fusion. Science 220 , 1300–1302 (1983).

    Article  CAS  Google Scholar 

  5. Wilmut, I., Schnieke, A.E., McWhir, J., Kind, A.J. & Campbell, K.H.S. Viable offspring derived from fetal and adult mammalian cells. Nature 385, 810–813 (1997).

    Article  CAS  Google Scholar 

  6. Cibelli, J.B. et al. Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science 280, 1256–1258 (1998).

    Article  CAS  Google Scholar 

  7. Campbell, K.H.S., McWhir, J., Ritchie, W.A., & Wilmut, I. Sheep cloned by nuclear transfer from cultured cell line. Nature 380, 64–66 ( 1996).

    Article  CAS  Google Scholar 

  8. Kato, Y. et al. Eight calves cloned from somatic cells of a single adult. Science 262, 2095–2098 ( 1998).

    Article  Google Scholar 

  9. Wakayama, T., Perry, A.C.F., Zuccotti, M., Johnson, K.R. & Yanagimachi, R. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 394, 369–374 ( 1998).

    Article  CAS  Google Scholar 

  10. Wakayama, T. & Yanagimachi, R. Cloning of male mice from adult tail-tip cells. Nat. Genet. 22, 127– 128 (1999).

    Article  CAS  Google Scholar 

  11. Baguisi, A. et al. Production of goats by somatic cell nuclear transfer. Nat. Biotechnol. 17, 456–461 (1999).

    Article  CAS  Google Scholar 

  12. Meng, L., Ely, J.J., Stouffer, R.L. & Wolf, D.P. Rhesus monkeys produced by nuclear transfer. Biol. Reprod. 57, 454–459 (1997).

    Article  CAS  Google Scholar 

  13. Bondioli, K.R. Nuclear transfer in cattle. Mol. Reprod. Dev. 36, 274–275 (1993).

    Article  CAS  Google Scholar 

  14. Shields, P.G. et al. Analysis of telomere lengths in cloned sheep. Nature 399, 316–317 (1999).

    Article  Google Scholar 

  15. Zawada, W.M. et al. Somatic cell cloned transgenic bovine neurons for transplantation in parkinsonian rats. Nat. Med. 4, 569– 574 (1998).

    Article  CAS  Google Scholar 

  16. Galton, D.J., Kay, A. & Cavanna, J.S. Human cloning: safety is the issue. Nat. Med. 4, 644 (1998).

    Article  CAS  Google Scholar 

  17. Renard, J.P. et al. Lymphoid hypoplasia and somatic cloning. Lancet 353, 1489–1491 (1999).

    Article  CAS  Google Scholar 

  18. Solter, D. & Gearhart, J. Putting stem cells to work. Science 283, 1468–1470 ( 1999).

    Article  CAS  Google Scholar 

  19. Weiss, R. Clone defects point to need for two genetic parents. Washington Post May 10 (1999), p 1.

  20. Pennis, E. After Dolly, a pharming frenzy. Science 279, 646–648 (1998).

    Article  Google Scholar 

  21. Walker, S.K., Hartwich, K.M. & Seamark, R.F. The Production of unusually large offspring following embryo manipulation—concepts and challenges. Theriogenology 45, 111 (1996).

    Article  Google Scholar 

  22. Cibelli, J.B. et al. Transgenic bovine chimeric offspring produced from somatic cell-derived stem-like cells. Nat. Biotechnol. 16, 642 –646 (1998).

    Article  CAS  Google Scholar 

  23. Robl, J., Cibelli, J. & Stice, S.L. Embryonic or stem-like cell lines produced by cross species nuclear transplantation. International Patent Application WO 98/07841. World Intellectual Property Organization (February 26, 1998).

  24. Dominko, T. et al. Bovine oocyte cytoplasm supports development of embryos produced by nuclear transfer of somatic cell nuclei from various mammalian species. Biol. Reprod. 60, 1496– 1502 (1999).

    Article  CAS  Google Scholar 

  25. Cummins, J. Mitochondrial DNA in mammalian reproduction. Rev. Reprod. 3, 172–182 (1998).

    Article  CAS  Google Scholar 

  26. Meirelles, F.V. et al. Zygote reconstructions among Bos indicus and Bos taurus cattle and consequences on mitochondrial inheritance. Theriogenology 51, 209 (1999).

    Article  Google Scholar 

  27. Kenyon, L. & Moraes, C.T. Expanding the functional human mitochondrial DNA database by the establishment of primate xenomitochondrial cybrids. Proc. Natl. Acad. Sci. USA 94, 9131–9135 (1997).

    Article  CAS  Google Scholar 

  28. Jones, M.J. & First, N.L. Expression of the cell cycle control protein CDC25 in cleavage stage bovine embryos. Zygote 3,133–139 (1995).

    Article  CAS  Google Scholar 

  29. Prather, R.S. Nuclear control of early embryonic development in the domestic pig. J. Reprod. Fertil. (Suppl) 48,17–29 (1993).

    CAS  Google Scholar 

  30. Crosby, I.M., Gandolfi, F. & Moor, R.M. Control of protein synthesis during early cleavage of sheep embryos. J. Reprod. Fertil. 82, 769–775 (1988).

    Article  CAS  Google Scholar 

  31. Braude, P., Bolton, V. & Moore, S. Human gene expression first occurs between the four- and eight-cell stages of preimplantation development. Nature 332, 459–461 (1988).

    Article  CAS  Google Scholar 

  32. Vogel, G. Harnessing the power of stem cells. Science 283, 1432–1434 (1999).

    Article  CAS  Google Scholar 

  33. Thomson, J.A. et al. Embryonic stem cell lines derived from human blastocytes. Science 282, 1145–1147 ( 1998).

    Article  CAS  Google Scholar 

  34. Klug, M.G., Soonpaa, M.H., Koh, G.Y. & Field, L.J. Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. J. Clin. Invest. 98, 216– 224 (1996).

    Article  CAS  Google Scholar 

  35. Pasternak, R.C. & Braunwald, E. in Harrison's principles of internal medicine, Edn. 12 (eds Wilson, J.D. et al. ) 953–964 (McGraw-Hill, New York, NY; 1991).

    Google Scholar 

  36. Lanza, R.P., Langer, R. & Vacanti, J.P. (eds). Principles of tissue engineering, Edn. 2. (Academic Press, San Diego, CA, in press).

  37. Lanza, R.P., Cibelli, J.B. & West, M.D. Human therapeutic cloning. Nat. Med. 5, 975–977 (1999).

    Article  CAS  Google Scholar 

  38. Lanza, R.P. et al. Science over politics. Science 283, 1849–1850 (1999).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Advanced Cell Technology, Worcester, 01605, MA

    Robert P. Lanza, Jose B. Cibelli & Michael D. West

Authors
  1. Robert P. Lanza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jose B. Cibelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael D. West
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert P. Lanza.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lanza, R., Cibelli, J. & West, M. Prospects for the use of nuclear transfer in human transplantation. Nat Biotechnol 17, 1171–1174 (1999). https://doi.org/10.1038/70709

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/70709

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing