Friday, 18 January 2008

Human Cloning Achieved?

Human Cloning Achieved? Friday, 18 January 2008 In a research paper from a group in La Jolla, CA and Detroit, MI, scientists describe how they have succeeded in producing a human cloned blastocysts, using freshly donated eggs and adult fibroblasts. Thorough analysis of the DNA and mtDNA in the donor cells and resulting blastocyst cells confirmed that SCNT had occurred. However, no stem cell lines were obtained from this single cloned blastomere, since all the material was used for the DNA analyses. Also, several other attempts to produce cloned embryos failed, not producing any live blastocysts or producing parthenogenetically activated blastocysts. Therefore, the value of the recent study is limited, even though it seams to confirm the possibility of producing cloned human embryos. The generation of patient-specific embryonic stem cells would revolutionize our understanding of human diseases (1). Currently, two different approaches are being studied to derive patient-specific stem cells: somatic cell nuclear transfer (SCNT) and direct reprogramming (2, 3). The recent generation of induced pluripotent stem (iPS) cells has put the feasibility of SCNT in regenerative medicine under intense discussion. However, at this early stage of development, the achievement to make iPS cells can not be considered as a substitute for SCNT. As has been pointed out by many scientists, the use of genes and retroviruses known to cause cancer in mammals and retroviruses known to have the ability to disrupt the normal DNA function and stimulate the birth of cancer cells (4, 5) makes it questionable if iPS cells can ever be used in regenerative medicine, especially cell therapy. Maybe the only use will be in research labs to elucidate small steps in the process of dedifferentiation or redifferentiation. Therefore it is essential to maintain the pace of research on the more ethically controversial areas, such as the use of fresh human oocytes and SCNT. Derivation of human embryos by SCNT remains in its infancy stages, with just a few papers reporting the generation of nuclear transfer human embryos (6-11). However, none of them have resulted in the derivation of nuclear transfer stem cells (NTSC). Clearly, still a number of hurdles, both ethical and technical, need to be overcome if SCNT is to lead to the successful application of patient-specific NTSC in regenerative medicine. In proving that human embryos can be obtained by SCNT, French et al. (12) succeeded in obtaining 5 blastocysts from 21 oocytes using adult somatic cells as karyoplasts. However, the results verified, for the first time through DNA and mtDNA fingerprinting that of the 5 blastocysts only one had the donor cell genomic DNA and the oocyte mtDNA. Considering such a small number of blastocysts, a completely different result may just as well have been reached. The experiment could easily have rendered zero true clones. The final challenge in therapeutic SCNT is still the isolation of NTSC. Once a NTSC line is obtained, a huge amount of cells will be available to carry out all the required studies to prove each clone identity. Firstly then, the process of finding way’s to explore patient-specific embryonic stem cells true potential in regenerative medicine, can start. REFERENCES 1. Cervera RP, Stojkovic M. Human embryonic stem cell derivation and nuclear transfer: impact on regenerative therapeutics and drug discovery. Clin Pharmacol Ther 2007;82:310-315. 2. Takahashi K, Tanabe K, Ohnuki M et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861-872. 3. Yu J, Vodyanik MA, Smuga-Otto K et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007;318:1917-1920. 4. Löwer R. The pathogenic potential of endogenous retroviruses: facts and fantasies. Trends Microbiol 1999;7:350-356. 5. Yi Y, Hahm SH, Lee KH. Retroviral gene therapy: safety issues and possible solutions. Curr Gene Ther 2005;5:25-35. 6. Cibelli JB, Kiessling AA, Cuniff K et al. Somatic cell nuclear transfer in humans: pronuclear and early embryonic development. J Reg Med 2001;2:25-31. 7. Lu C, Lin G, Xie X et al. Reconstruction of human embryos derived from somatic cells. Chin Science Bull 2003;48:1840-1843. 8. Stojkovic M, Stojkovic P, Leary C et al. Derivation of a human blastocyst after heterologous nuclear transfer to donated oocytes. Reprod Biomed Online 2005;11:226-231. 9. Lavoir MC, Weier J, Conaghan J et al. Poor development of human nuclear transfer embryos using failed fertilized oocytes. Reprod Biomed Online 2005:11:740-744. 10. Hall VJ ,Compton D, Stojkovic P et al. Developmental competence of human in vitro aged oocytes as host cells for nuclear transfer. Hum Reprod 2007;22:52-62. 11. Heindryckx B, De Sutter P, Gerris J et al. Embryo development after successful somatic cell nuclear transfer to in vitro matured human germinal vesicle oocytes. Hum Reprod 2007;22:1982-1990. 12. French AJ, Adams CA, Anderson LS et al. Development of human cloned blastocysts following somatic cell nuclear transfer (SCNT) with adult fibroblasts. Stem Cells 2008; January 17, doi:10.1634/stemcells.2007-0252 ......... ZenMaster

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