(1/24) The subsidiarity principle in the context of embryonic stem cell research.
Embryonic stem cell research is regulated by different forms of the subsidiarity principle, i.e. research on embryos should only be conducted if no suitable alternatives exist. Four types are discussed: animal versus human material, adult versus embryonic stem cells, affected or at risk embryos versus healthy embryos, and supernumerary versus research embryos. Three major arguments regarding the subsidiarity principle are discussed: the necessity argument, the least offensive moral approach and the 'nothing is lost' argument. It is proposed that the burden of proof should be shifted onto those who oppose embryonic research. When the freedom of research and the moral obligation to relieve human suffering is taken seriously, the opponents of this research should first demonstrate that embryonic stem cells do not work or that adult stem cells work better. (+info)
(2/24) The knockout mouse project.
Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain. (+info)
(3/24) Embryonic death and the creation of human embryonic stem cells.
The creation of human embryonic stem cells through the destruction of a human embryo pits the value of a potential therapeutic tool against that of an early human life. This contest of values has resulted in a polarized debate that neglects areas of common interest and perspective. We suggest that a common ground for pursuing research on human embryonic stem cells can be found by reconsidering the death of the human embryo and by applying to this research the ethical norms of essential organ donation. (+info)
(4/24) A perspective on stem cells by a clinician.
Stem cell terminology has entered the lexicon of medical practitioners even though the application of harvesting stem cells to treat diseases other than haematological disorders is not yet a reality in clinical practice. All branches of medicine will be affected by the new technology, more so those related to regenerative cell-based therapy for disorders such as Parkinson's disease, Alzheimer's disease, multiple sclerosis and traumatic injuries to the nervous system. Endocrinology is not a branch of medicine that carries a burden of disease that merits priority for the early application of stem cell therapy once the technique becomes safe and practical to do so. However, the allied disorder of diabetes is, sine qua non, an ideal example of how stem cell therapy has the potential to cure a chronic disabling condition. It is logical therefore to have included a number of articles on stem cells in this special issue of this journal, publishing papers on a range of endocrine-related topics. (+info)
(5/24) Creating and sacrificing embryos for stem cells.
The compromise position that accepts the use and derivation of stem cells from spare in vitro fertilisation embryos but opposes the creation of embryos for these purposes is a very weak ethical position. This paper argues that whatever the basis is on which defenders of this viewpoint accord intrinsic value to the embryo, once they accept the creation and sacrifice of embryos to benefit infertile people with a child-wish, they do not have a sound moral argument to condemn the creation and sacrifice of embryos to benefit ill and injured people. (+info)
(6/24) Equivalency of nuclear transfer-derived embryonic stem cells to those derived from fertilized mouse blastocysts.
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. (+info)
(7/24) Reprogramming efficiency following somatic cell nuclear transfer is influenced by the differentiation and methylation state of the donor nucleus.
Reprogramming of a differentiated cell nucleus by somatic cell nuclear transplantation is an inefficient process. Following nuclear transfer, the donor nucleus often fails to express early embryonic genes and establish a normal embryonic pattern of chromatin modifications. These defects correlate with the low number of cloned embryos able to produce embryonic stem cells or develop into adult animals. Here, we show that the differentiation and methylation state of the donor cell influence the efficiency of genomic reprogramming. First, neural stem cells, when used as donors for nuclear transplantation, produce embryonic stem cells at a higher efficiency than blastocysts derived from terminally differentiated neuronal donor cells, demonstrating a correlation between the state of differentiation and cloning efficiency. Second, using a hypomorphic allele of DNA methyltransferase-1, we found that global hypomethylation of a differentiated cell genome improved cloning efficiency. Our results provide functional evidence that the differentiation and epigenetic state of the donor nucleus influences reprogramming efficiency. (+info)
(8/24) Mitochondrial distribution and microtubule organization in fertilized and cloned porcine embryos: implications for developmental potential.
Mitochondrial distribution and microtubule organization were examined in porcine oocytes after parthenogenesis, fertilization and somatic cell nuclear transfer (SCNT). Our results revealed that mitochondria are translocated from the oocyte's cortex to the perinuclear area by microtubules that either constitute the sperm aster in in vitro-fertilized (IVF) oocytes or originate from the donor cell centrosomes in SCNT oocytes. The ability to translocate mitochondria to the perinuclear area was lower in SCNT oocytes than in IVF oocytes. Sperm-induced activation rather than electrical activation of SCNT oocytes as well as the presence of the oocyte spindle enhanced perinuclear mitochondrial association with reconstructed nuclei, while removal of the oocyte spindle prior to sperm penetration decreased mitochondrial association with male pronuclei without having an apparent effect on microtubules. We conclude that factors derived from spermatozoa and oocyte spindles may affect the ability of zygotic microtubules to translocate mitochondria after IVF and SCNT in porcine oocytes. Mitochondrial association with pronuclei was positively related with embryo development after IVF. The reduced mitochondrial association with nuclei in SCNT oocytes may be one of the reasons for the low cloning efficiency which could be corrected by adding yet to be identified, sperm-derived factors that are normally present during physiological fertilization. (+info)