Development to term of a cloned offspring derived from an embryo created by somatic cell nuclear transfer is a remarkable demonstration of adult cellular plasticity. Reconstruction of embryos by transfer of human cells into enucleated oocytes (therapeutic cloning) is one potential source of pluripotent embryonic stem (ES) cells for cell replacement therapy. Furthermore, ES cell lines that are derived by this method should be histocompatible with the patient who supplied the donor cells. In addition, therapeutic cloning from diseased individuals will provide ES cell lines that can be used as in vitro cellular models for research purposes. In animal reproductive cloning (i.e., creation of an entire offspring), nuclei from a variety of tissues have been used for transfer into metaphase Il-arrested enucleated oocytes, although the success rate is very low. Losses occur throughout the process, from the nuclear transfer procedure; from poorly developed embryos, loss of fetuses, and death at birth or newborns within 24 h; as well as from premature postnatal death. Development of viable individuals from nuclear transfer is typically between 1 and 4%; nevertheless, therapeutic cloning requires development only to the 6-day embryo stage, and thus we should expect efficiency to be greater. The results from animal reproductive cloning studies have revealed important aspects about the nuclear transfer process. The task of the oocyte in reprogramming a diploid somatic cell nucleus is a formidable one, and it is not surprising that the success rate is low. Abnormalities in DNA methylation patterns of the chromatin have been found in cloned embryos. Considering that epigenetic changes may be associated with development of cancers, care must be taken to screen for the dysprogramming of genes in ES lines derived from cloned embryos. Thus, although the therapeutic promise is very great, the safety of transplanted cloned cells must be assessed. In addition, the creation of in vitro cellular models of disease by therapeutic cloning will provide an exceptional tool for research and drug screening.
6.1. INTRODUCTION et al., 2002). These demonstrations show the vast potential of cell
Human stem cells offer great potential for lifelong treatment of deteriorating and debilitating diseases such as Parkinson's disease, diabetes, multiple sclerosis, and heart disease. There are primarily two stem cell sources available: those derived from embryos and those derived from adult tissues (including the umbilical vein).
replacement therapy in humans.
Investigations carried out using stem cells in mice have revealed their powerful therapeutic capabilities. Transfer of adult neural stem cells (Teng et al., 2002) and neural differentiated embryonic cells (McDonald et al., 1999) into spinal cord injury in rats resulted in hind-limb weight bearing, stepping, and enhanced coordination. Oligodendrocytes and insulin-secreting cells, both derived from embryonic stem (ES) cells, replaced lost myelin in rat spinal cords (Liu et al., 2000) and normalized glycemia in diabetic mice (Soria et al., 2000), respectively. In addition, following transplantation of partially differentiated mouse ES cells into the rat model of Parkinson's disease, approximately half of the rats with surviving grafts contained dopamine neurons (Bjorklund
From: Stem Cells Handbook
Edited by: S. Sell © Humana Press Inc., Totowa, NJ
6.1.1. ADULT AND ES CELLS There are advantages and disadvantages of obtaining stem cells from adult sources or embryos as sources for therapy (see Table 1). ES cells are pluripo-tent, immortal cell lines derived from the inner cell mass (ICM) of embryos, with the potential to differentiate into cells from all three embryonic lineages, even after prolonged culture (Thomson et al., 1998). Adult stem cells reside in certain tissues of the body and exist to replenish the tissues in which they reside. These cells show limited differentiation potential and are therefore said to be multipotent. However, the plasticity of these stem cells lines is potentially much greater than previously believed, and investigations have shown that adult stem cells can "transdifferentiate" into cells of different embryonic lineages: from muscle to blood and vice versa, from blood to liver, and from brain to blood and muscle (For a review, see Clarke and Frisen, 2001). Nevertheless, recent publications have highlighted the need for caution in interpretation of the apparent plasticity of adult stem cells. Two independent groups cultured mouse ES cells alongside mouse brain (Ying et al., 2002) and bone marrow cells (Terada et al., 2002). Both sets of results showed that apparently reprogrammed adult cells were
Comparison of Embryo and Adult Stem Cell Sources
Comparison of Embryo and Adult Stem Cell Sources
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