Somatic cell nuclear transfer

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Human embryonic stem cell colony on MEF - feeder cells .

The somatic cell nuclear transfer (Engl. Somatic cell nuclear transfer , SCNT) referred to in the genetics of the transfer of a nucleus in a seedless cell for the purpose of cloning . Somatic cell nuclear transfer is a form of asexual reproduction and one of the three methods of generating induced pluripotent stem cells . Somatic cell nucleus transfer is the only method of generating pluripotent stem cells from dead tissue , such as B. frozen or lyophilized tissue. If the egg cell and the cell nucleus come from two different species , it is a cytoplasmic hybrid , or cybrid for short .

principle

The nucleus of a cell contains the DNA of an organism , which serves as a template. When removing the nucleus from one cell and replacing it with a nucleus from another cell, the template from one cell is transferred to another. The cell and all cells that are derived from it through cell division therefore change.

Problems

Since the stress for the cell and the cell nucleus is enormous, this process leads to a high death rate for the recipient cells. This process cannot currently be automated and must be carried out manually under a microscope , which is very time-consuming. The discharge rate is low due to incomplete epigenetic reprogramming in the egg cell . Errors in the formation of the placenta often occur , such as B. placentomegaly, decreased vascularization , hypoplasia of the trophoblastic epithelium, and above average fetal growth.

Because the donor cell is a body cell , it has to be artificially “activated” in order to be able to work as a fertilized egg cell , because it should then grow into a whole organism. The biochemical processes leading to activation are not yet fully understood at this point in time.

Ethical aspects

Human blastocyst with the inner cell mass (top right).

The Ethics Committee of the American Society for Reproductive Medicine rejects the SCNT as unethical for the treatment of infertility due to safety concerns, unknown effects on children, families, and society, and more ethical alternatives to assistive reproductive medicine.

The same methodology for treating infertility with SCNT can also be used for reproductive cloning . Organizations against reproductive cloning have been set up in the United States. Some American scientists argued for the SCNT that the clone produced was not yet a human embryo according to the legal situation there. Furthermore, the SCNT is carried out in human egg cells , which previously had to be removed first, with the risk of ovarian hyperstimulation syndrome . Excess embryos produced may not be destroyed in Germany, since the destruction of embryos is legally treated as murder. Furthermore, the commercial trade in human egg cells is considered unethical. Therefore, it is currently being investigated to create egg cells from iPS .

A possible benefit of the SCNT is the generation of mostly autologous cell lines for adoptive cell transfer in patients to replace defective or insufficient cell types . The genomic DNA of these cells is identical to that of the recipient; the mtDNA comes from the egg donor.

Legal position

The Council of Europe's Convention on Human Rights and Biomedicine and the Additional Protocol to the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine, on the Prohibition of Cloning Human Being, prohibit SCNT in humans . So far 31 of the 45 member states have signed the drafts of the Convention and 18 of them have adopted them. The additional protocol was signed by 39 member states and ratified by 14.

In the UK, the SCNT is eligible for research approval under the Human Fertilization and Embryology Act 1990 as amended by the Human Fertilization and Embryology Authority .

The SCNT is legal in the United States. In 2002, however, a moratorium on state research funding for the SCNT was decided.

In 2003 the United Nations adopted a proposal from Costa Rica banning all forms of human cloning because it was incompatible with human dignity and the protection of human life. Depending on the legal interpretation, this passage also includes the SCNT.

history

Nuclear transfer was first considered in 1895 by Yves Delage . The methodical procedure was proposed in 1924 by Hans Spemann . In 1935 he received the Nobel Prize in Physiology or Medicine , and in 1938 he expanded his methodological proposals one last time. However, the methods were not sufficiently developed until 1952, when the nuclei of embryonic cells were transferred to frogs by Robert Briggs and Thomas J. King . John Gurdon was able to show the complete reprogramming of the transplanted cell nuclei, i.e. H. induced pluripotent stem cells from which all cell types could develop could be obtained from the differentiated cells . In 2012, John Gurdon was awarded the Nobel Prize in Physiology or Medicine.

The first publication of a somatic cell nuclear transfer in mammals was made in 1981 by Karl Illmensee . However, these results could not be reproduced . The sheep Dolly , cloned by Keith Campbell and Ian Wilmut , was the first known case of a cloned mammal in 1997. However, it was only in 2002 that Rudolf Jaenisch proved that there was no genetic information in the enucleated donor egg cells and that the reprogramming by the transplanted cell nucleus was not present took place.

On May 15, 2013 it was reported in Cell that it was possible for the first time to obtain pluripotent human stem cells from donor cells of children by means of cell nucleus transfer and to develop them into specialized cells of the pancreas as well as blood, heart, liver and nerve cells. In 2014, the first successful SCNT with human cell nuclei from adults was carried out. In January 2018, it was announced that Chinese scientists at the Institute of Neuroscience of the Chinese Academy of Sciences in Shanghai had succeeded in cloning monkeys for the first time. Two long-tailed macaques were born.

Web links

Individual evidence

  1. ↑ Lütjen-Drecoll E., ea: Functional Embryology: The Development of Functional Systems of the Human Organism , Schattauer Verlag, 2006, p. 171, ISBN 3794524519 , here online
  2. ^ S. Yamanaka, HM Blau: Nuclear reprogramming to a pluripotent state by three approaches. In: Nature (2010), Vol. 465 (7299), pp. 704-12. PMID 20535199 ; PMC 2901154 (free full text).
  3. ↑ S. Wakayama, T. Wakayama: Improvement of mouse cloning using nuclear transfer-derived embryonic stem cells and / or histone deacetylase inhibitor. In: Int J Dev Biol. (2010), Vol. 54 (11-12), pp. 1641-8. PMID 21404185 .
  4. ↑ Marieke Degen , Monika Seynsche : The human being in the animal - German Ethics Council comments on research on so-called hybrid beings . In: dradio.de, Deutschlandfunk, Forschung aktuell , September 27, 2011, accessed on October 26, 2018.
  5. ↑ C. Palmieri, P. Loi, G. Ptak, L. Della Salda: Review paper: a review of the pathology of abnormal placentae of somatic cell nuclear transfer clone pregnancies in cattle, sheep, and mice. In: Vet Pathol. (2008), Vol. 45 (6), pp. 865-80. PMID 18984789 .
  6. ↑ P. Chavatte-Palmer, S. Camous, H. Jammes, N. Le Cleac'h, M. Guillomot, RS Lee: Review: Placental perturbations induce the developmental abnormalities often observed in bovine somatic cell nuclear transfer. In: Placenta (2012), Vol. 33 Suppl, pp. S99-S104. PMID 22000472 .
  7. ↑ Ethics Committee of the American Society for Reproductive Medicine: Human somatic cell nuclear transfer and cloning. In: Fertility and sterility. Volume 98, Number 4, October 2012, pp. 804-807, ISSN  1556-5653 . doi : 10.1016 / j.fertnstert.2012.06.045 . PMID 22795681 .
  8. ↑ Lori B. Andrews et al. (March 19, 2002). "Open Letter to US Senators on Human Cloning and Eugenic Engineering". ( Memento of the original from September 30, 2006 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. Retrieved August 7, 2006. @1@ 2Template: Webachiv / IABot / genetics-and-society.org
  9. ↑ Jeremy Rifkin. (February 18, 2002). Fusion Biopolitics . The Nation . Retrieved August 7, 2006.
  10. ^ Sheryl Gay Stolberg, " Some for Abortion Rights Lean Right in Cloning Fight, " New York Times . Retrieved August 7, 2002.
  11. ↑ Lori B. Andrews, et al., Open Letter to US Senate on Human Cloning ( Memento of the original dated November 22, 2010 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. , (March 19, 2002) @1@ 2Template: Webachiv / IABot / geneticsandsociety.org
  12. ^ Cunningham, Thomas V. (2013): "What justifies the United States ban on federal funding for nonreproductive cloning?" Medicine, Health Care and Philosophy, vol. 16, n. 4, pp. 825-841.
  13. ^ Council of Europe, Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (April 4, 1997, accessed October 6, 2006); Council of Europe, Additional Protocol to the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine, on the Prohibition of Cloning Human Being (January 12, 1998, accessed October 6, 2006 )
  14. ^ Andy Coghlan, " Cloning opponents fear loopholes in new UK law, " New Scientist (November 23, 2001, accessed October 6, 2006)
  15. ↑ Chapter 5: Legal and Policy Considerations. Cloning Human Beings ( Memento of July 6, 2007 in the Internet Archive ), Report and Recommendations of the National Bioethics Advisory Commission, June 1997. Accessed 21 Oct 06
  16. ^ Robertson, John A. (2010): "Embryo Stem Cell Research: Ten Years of Controversy". The Journal of Law, Medicine, & Ethics, vol. 38. n.2 pp. 191-203.
  17. ↑ United Nations, " General Assembly Adopts United Nations Declaration on Human Cloning By Vote of 84-34-37 ", press release (August 3, 2005, accessed October 6, 2006)
  18. ↑ Jean-Claude C. Beetschen, Jean-Louis L. Fischer: Yves Delage (1854-1920) as a Forerunner of Modern Nuclear Transfer Experiments. In: International Journal of Developmental Biology (2004), Vol. 48, pp. 607-12. PMID 15470632 . PDF .
  19. ↑ Hans Spemann, Hilde Mangold: About induction of embryonic systems by implantation of foreign organizers . In arch. Micr. Anat. And development mech. (1924), Vol. 100, pp. 599-638
  20. ^ Nobel Lectures, Physiology or Medicine 1922-1941 , Elsevier Publishing Company, Amsterdam, 1965
  21. ^ Hans Spemann: Embryonic Development and induction , Hafner Publ. Co., New York 1962, reprint from 1938.
  22. ^ R. Briggs, TJ King: Transplantation of Living Nuclei From Blastula Cells into Enucleated Frogs' Eggs . In: Proc Natl Acad Sci USA (1952), Vol. 38 (5), pp. 455-63. PMID 16589125 ; PMC 1063586 (free full text).
  23. ^ Maria A. Di Berardino, Robert G. McKinnell: The Pathway to Animal Cloning and Beyond - Robert Briggs (1911-1983) and Thomas J. King (1921-2000). In: Journal of Experimental Zoology Part a-Comparative Experimental Biology (2004), Vol. 301A, pp. 275-9. PMID 15039985 .
  24. ↑ John B. Gurdon, TR Elsdale, M. Fischberg: Sexually mature individuals of Xenopus laevis from the transplantation of single somatic nuclei . In: Nature (1958), vol. 182 (4627), pp. 64-5. PMID 13566187 .
  25. ^ John Gurdon: Nuclear reprogramming in eggs . In: Nat Med. (2009), Vol. 15 (10), pp. 1141-4. PMID 19812574 .
  26. ^ I. Wilmut, AE Schnieke, J. McWhir, AJ Kind, KH Campbell: Viable offspring derived from fetal and adult mammalian cells. In: Nature (1997) 385 : 810-3 (6619). Erratum in: Nature 1997, Vol. 386 (6621), p. 200. PMID 9039911 .
  27. ↑ Konrad Hochedlinger, R. Jaenisch: Monoclonal mice generated by nuclear transfer from mature B and T donor cells . In: Nature (2002), 415 : 1035-8 (6875). PMID 11875572 .
  28. ↑ Masahito Tachibana et al .: Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer. In: Cell . Online publication from May 15, 2013, doi: 10.1016 / j.cell.2013.05.006
  29. ↑ Young Gie Chung, Jin Hee Eum, Jeoung Eun Lee, Sung Han Shim, Vicken Sepilian, Seung Wook Hong, Yumie Lee, Nathan R. Treff, Young Ho Choi, Erin A. Kimbrel, Ralph E. Dittman, Robert Lanza, Dong Ryul Lee: Human Somatic Cell Nuclear Transfer Using Adult Cells. In: Cell Stem Cell (online pre-release). doi : 10.1016 / j.stem.2014.03.015 .
  30. ↑ Zhen Liu, Yijun Cai, Yan Wang, Yanhong Nie, Chenchen Zhang: Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer . In: Cell . tape 0 , no. 0 , ISSN  0092-8674 , doi : 10.1016 / j.cell.2018.01.020 ( cell.com [accessed January 26, 2018]).
  31. ↑ David Cyranoski: First monkeys cloned with technique that made Dolly the sheep . January 24, 2018, doi : 10.1038 / d41586-018-01027-z ( nature.com [accessed January 26, 2018]).
  32. ↑ Dennis Normile: These monkey twins are the first primate clones made by the method that developed Dolly . In: Science . January 24, 2018 ( sciencemag.org [accessed January 27, 2018]).