Therapeutic cloning by xenotransplanted oocytes, supplemented with species specific reprogramming factors
ABSTRACT For therapeutic medication, a lot of work has been done regarding human embryonic stem (ES) cell lines derivation, but immunorejection is a major dilemma of this cell based therapy. Since long time, derivation of patient matched stem cells have been hoped to overcome this problem. Oocytes after nuclear transfer are the most reliable source for patient matched ES cells derivation, for therapeutic use. In humans, utilization of oocytes for stem cell research raises sensitive logistical and ethical questions; primarily surrounding participation of women as oocyte donors. It has been claimed that therapeutic cloning would lead to commercial exploitation of poor women. On the other hand, the therapeutic promise of embryonic stem cell is so huge that there is a strong incentive to find some alternate sources of human oocytes. Here we propose to utilize the cross species oocytes supplemented with human ES cellular extracts to establish patient specific ES cell lines.
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ABSTRACT: Cloning mammals by nuclear transfer is a powerful technique that is quickly advancing the development of genetically defined animal models. However, the overall efficiency of nuclear transfer is still very low and several hurdles remain before the power of this technique will be fully harnessed. Among these hurdles include an incomplete understanding of biologic processes that control epigenetic reprogramming of the donor genome following nuclear transfer. Incomplete epigenetic reprogramming is considered the major cause of the developmental failure of cloned embryos and is frequently associated with the disregulation of specific genes. At present, little is known about the developmental mechanism of reconstructed embryos. Therefore, screening strategies to design nuclear transfer protocols that will mimic the epigenetic remodeling occurring in normal embryos and identifying molecular parameters that can assess the developmental potential of pre-implantation embryos are becoming increasingly important. A crucial need at present is to understand the molecular events required for efficient reprogramming of donor genomes after nuclear transfer. This knowledge will help to identify the molecular basis of developmental defects seen in cloned embryos and provide methods for circumventing such problems associated with cloning the future application of this technology.Reproductive Biology and Endocrinology 12/2003; 1:84. DOI:10.1186/1477-7827-1-84 · 2.41 Impact Factor
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ABSTRACT: The maternal-to-zygotic transition (MZT) is a universal step in animal development characterized by two major events: activation of zygotic transcription and degradation of maternally provided mRNAs. How zygotic gene products instruct the degradation of maternal messages remains a long-standing question in biology. MicroRNAs (miRNAs) have recently emerged as widespread regulators of gene expression. miRNAs control temporal and spatial gene expression by both accelerating the decay of mRNAs from previous developmental stages and modulating the levels of actively transcribed genes. In this review, I discuss recent studies of the roles of miRNAs during the maternal-to-zygotic transition and cellular reprogramming, where they reshape transcriptional landscapes to facilitate the establishment of novel cellular states.Current opinion in genetics & development 05/2010; 20(4):369-75. DOI:10.1016/j.gde.2010.04.003 · 8.57 Impact Factor
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ABSTRACT: It is thought that most cell types of the human body share the same genetic information as that contained in the zygote from which they originate. Consistent with this view, animal cloning studies demonstrated that the intact genome of a differentiated cell can be reprogrammed to support the development of an entire organism and allow the production of pluripotent stem cells. Recent progress in reprogramming research now points to an important role for transcription factors in the establishment and the maintenance of cellular phenotypes, and to cell division as a mediator of transitions between different states of gene expression.Nature Reviews Molecular Cell Biology 08/2008; 9(7):505-16. DOI:10.1038/nrm2439 · 36.46 Impact Factor