Experiment reveals deficits in european regulation
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The derivation of embryonic stem (ES) cells by nuclear transfer holds great promise for research and therapy but involves the destruction of cloned human blastocysts. Proof of principle experiments have shown that 'customized' ES cells derived by nuclear transfer (NT-ESCs) can be used to correct immunodeficiency in mice. Importantly, the feasibility of the approach has been demonstrated recently in humans, bringing the clinical application of NT-ESCs within reach. Altered nuclear transfer (ANT) has been proposed as a variation of nuclear transfer because it would create abnormal nuclear transfer blastocysts that are inherently unable to implant into the uterus but would be capable of generating customized ES cells. To assess the experimental validity of this concept we have used nuclear transfer to derive mouse blastocysts from donor fibroblasts that carried a short hairpin RNA construct targeting Cdx2. Cloned blastocysts were morphologically abnormal, lacked functional trophoblast and failed to implant into the uterus. However, they efficiently generated pluripotent embryonic stem cells when explanted into culture.
Therapeutic cloning, whereby nuclear transfer (NT) is used to generate embryonic stem cells (ESCs) from blastocysts, has been demonstrated successfully in mice and cattle. However, if NT-ESCs have abnormalities, such as those associated with the offspring produced by reproductive cloning, their scientific and medical utilities might prove limited. To evaluate the characteristics of NT-ESCs, we established more than 150 NT-ESC lines from adult somatic cells of several mouse strains. Here, we show that these NT-ESCs were able to differentiate into all functional embryonic tissues in vivo. Moreover, they were identical to blastocyst-derived ESCs in terms of their expression of pluripotency markers in the presence of tissue-dependent differentially DNA methylated regions, in DNA microarray profiles, and in high-coverage gene expression profiling. Importantly, the NT procedure did not cause irreversible damage to the nuclei. These similarities of NT-ESCs and ESCs indicate that murine therapeutic cloning by somatic cell NT can provide a reliable model for preclinical stem cell research.
Almost all decisions with regard to allowing or forbidding research with and on the embryo as well as any other diagnostic invasion into the embryo depend on what kind and range of protection human life in this early stage of its development is or should be entitled to. This question is commonly referred to as that of the 'moral status' of the embryo or-with special regard to legal provisions and sanctions-as its 'legal status'. The answer to this fundamental question, however, is much debated and highly controversial, both nationally and internationally. Therefore professional and legal regulations range from the rather permissive (as in the new English Human Fertilization and Embryology Act of 1990) on the one hand to the total prohibition of embryo research or certain reproductive procedures on the other (as has recently been enacted by the German Embryo Protection Act of 1990). Thus, trying to reach consensus with regard to an embryo's legal/ethical right to protection is made all the more difficult because such an opinion is often, consciously or unconsciously, prejudiced by the desire to give researchers either more or less freedom of action, depending on one's point of view: Those who wish to see diagnostic or other experimental procedures with embryos facilitated, are inclined to deny their human quality from the very start. They base their arguments on the lack of individual personality in the preinidation phase of development, or simply on the fact that in many countries abortion is not illegal at that stage. Those who, on the contrary, find abortion as well as embryo research indefensible, believe their position well-founded by assuming that the embryo, from the time of fertilization, has the individuality and personality of a human being and thus is entitled to its own basic legal rights. Since to me neither of these extreme positions seems to be particularly cogent, I will try in this article to show the reasons for and consequences of adopting a middle course which neither leaves the embryo at free disposition nor bars any kind of diagnostic or other scientific invasion.
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Cloning from adult somatic cells has been successful in at least ten species. Although generating viable cloned mammals from adult cells is technically feasible, prenatal and perinatal mortality is high and live cloned offspring have had health problems. This chapter summarizes the health consequences of cloning in mice and discusses possible mechanisms through which these conditions may arise. These studies have further significance as other assisted reproductive techniques (ART) also involve some of the same procedures used in cloning, and there are some reports that offspring generated by ART display aberrant phenotypes as well. At the moment, the long-term consequences of mammalian cloning remain poorly characterized. Data available thus far suggest that we should use this technology with great caution until numerous questions are addressed and answered.
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