hES cells because there will be differences between ES cells of different species. Studies of nonhuman ES cell models and of hES cells must proceed in parallel.

  • A related challenge will be the development of methods to separate progenitors of restricted developmental potential from hES cells (or methods to ensure complete conversion of hES cells into the desired cellular derivatives). mES cells transplanted to ectopic sites can generate benign tumors and such an outcome clearly would be undesirable in any cellular therapy. One can imagine methods for separating or removing persisting hES cells (such as sorting of undifferentiated cells or inducible suicide of inappropriate cells), but research will be required to ensure that such methods are effective.

  • All the foregoing procedures will necessitate means of testing the potential of the derived cells to contribute usefully when implanted and for adverse side effects; such tests will undoubtedly be required by FDA before any therapeutic use. That requirement will necessitate development of protocols for effective and ethical testing of the potential of hES cells and their derivatives (or adult stem cells). Many tests can be conducted in vitro but in vivo tests will also be mandatory. As discussed above, some such tests present no particular ethical problems, and the technical issues can be addressed with further experimentation. However, some chimera experiments that can be easily envisaged raise issues pertaining to the possibilities of hES cell contributions to the brain or the germline. Research is needed to determine the likelihood of those potential concerns. It has been argued that their potential may be quite limited but a main purpose of developing hES cell-based therapies is to promote some participation of the implanted cells. Research will be necessary to discover the extent to which this is possible both to exploit the therapeutic potential and to avoid undesired contributions.

  • One issue arising in any cell or tissue transplantation is immune rejection due to histocompatibility antigenic differences between people. This problem is confronted every day in organ transplantation and has been addressed with tissue-matching and immune suppression. Nevertheless it remains a problem and will affect any stem cell-based therapies (adult or embryonic) unless means can be found to avoid it. One such means is the use of autologous hES cells derived using a patient’s own nuclei to generate genetically identical hES cells through NT. That approach is feasible and likely to be exploited, but it will face hurdles, such as oocyte availability, if it is to be widely used. The more genetically diverse hES cells there are available, the more likely that a histocompatible matching line can be found. That is a strong argument for development of stem cell banks (see Chapter 5). In parallel, research into ways of avoiding immune rejection should be encouraged both for standard organ transplantation and for future hES cell therapies. With ES cells and their derivatives, it may be possible to devise means



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