The extensive background of knowledge on mouse embryo-derived stem cells provides an experimental model for human ES cell research and a means of testing ideas on the biological basis of therapeutic interventions involving stem cells. Given the extensive database of genomic and developmental information and the long history of mutagenesis and ES cell experimentation, the mouse is the ideal model organism for this purpose. The differentiation pathways leading to many specific cell types have been elucidated for stem cells in vitro and are supported by studies on developmental potential as assayed through contribution in vivo (reviewed by Odorico et al., 2001). Even highly organized structures such as insulin-expressing cells with the three-dimensional structure of pancreatic islets have been differentiated from ES cells, demonstrating their potential for the assembly of functional organs (Lumelsky et al., 2001). The feasibility of using ES cells to effect cures through tissue transplantation has been tested and validated (Soria et al., 2000). Through the manipulation of histocompatibility genes, mouse stem cells can be engineered to escape the immune response (Grusby et al., 1993).
With the advent of cloning mammals by nuclear transplantation into enucleated egg cytoplasm, another technical innovation to avoid immune rejection is being tested in mice. Embryos cloned by nuclear transfer of somatic cell nuclei have been used as a source for the derivation of new ES cell lines that retain full developmental potential (Munsie et al., 2000; Wakayama et al., 2001). Using this method, unique ES cell lines could be "tailor made" through cloning from a donor's somatic nuclei for eventual stem cell therapy of that same donor. Because the nuclear material originated with the donor, there would be no danger of immune rejection (Rideout et al., 2002) (Fig. 7). Studies like these demonstrate the potential for therapeutic uses of stem cells, and it is through the use of mouse stem cells that the strategies and therapies can be developed with a view to possible application to humans.
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