developed with the same ESCs would not, in theory, be rejected by the recipient because the immune cells produced in the recipient’s blood by the HSCs would see the implant tissue as “self”.

But that is a long way off, as Marcus Grompe noted, in as much as no one has yet demonstrated any in vivo reconstitution of an organ’s function in either humans or experimental animals with cells derived from human ESCs. Moreover, ESCs in tissue culture give rise to a mixture of cell types all at once, and biochemical, tissue-culture, and molecular-biology techniques to control and limit differentiation require much further investigation.

Because human ESCs have only recently become available for research, and because public funding for such research has been limited, studies of how well ESCs or their differentiated tissues perform physiologic functions has been largely conducted with mouse models. Ron McKay described progress made in coaxing the in vitro differentiation of human ESCs into insulin-producing cells that might be useful in treating diabetes, but he also noted that studies have already been conducted with analogous mouse cells transplanted into mice that have diabetes and that partial restoration of insulin regulation was observed (Lumelsky et al., 2001). Other studies have demonstrated that mouse ESCs can be successfully transplanted into rodents that have Parkinson’s disease symptoms and partially relieve these symptoms (Studer et al., 1998). Similarly, studies suggest that mouse ESCs can be transplanted into animals that have spinal-cord injuries and partially restore neural function (McDonald et al., 1999).

Those studies provide promise, but not definitive evidence, that similar treatments could be effective in humans. Human ESCs will need to be tested in primate models, such as those for Parkinson’s disease and diabetes mellitus in the rhesus monkey. Methods for transplanting ESCs need to be developed, as do means of establishing whether the cells develop and function properly after transplantation. In some cases, it will be important to ensure that the transplanted cells or tissues are incorporated and positioned properly relative to existing tissues, such as in heart and neural tissue; the three-dimensional, cell-to-cell interactions



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