significant tumor formation (Odorico et al., 2001). Obviously, this is a critical problem to understand and control.

It is too early to tell, therefore, whether it will be appropriate to use human ESCs directly in regenerative medicine. A great deal obviously must be elucidated about how the body controls the differentiation of stem cells, and this has yet to be reliably reproduced in vitro. Also, the behavior of ESCs implanted in a specific organ has not been well studied. It might someday be possible to add growth factors with a transplant to stimulate the production of a particular cell type or multiple cell types. “Inducer tissues” that interact with stem cells might be cotransplanted with ESCs to achieve a similar result. Those possibilities are still in experimental investigation.

In another respect, the possible problems associated with ESC transplantation are common to all transplantation, such as the risk of infection and the risk of tissue rejection. As discussed in Chapter 2, rejection is a serious obstacle to successful transplantation of stem cells and tissues derived from them. It has been suggested that ESCs provoke less of an immune reaction than a whole-organ transplant, but it is unclear whether that will be true of the regenerated tissues derived from ESCs. Some types of cells (such as dendritic cells, immune system cells, and vascular endothelial cells) carry more of the histocompatibility antigens that provoke immune reactions than other cells. Those types are present in the tissues of whole organs; they connect an organ with the bloodstream and nervous system. However, tissue derived in vitro from ESCs, such as liver tissue, would not contain such cells and therefore would theoretically trigger a milder immune response; this assumes that techniques for controlling differentiation of ESCs will be available. In addition, the liver cells likely would not be devoid of all surface antigens, and so, in the absence of other techniques to reduce transplant rejection, the use of immunosuppressive drugs will still have to be used, with attendant risks of infection and toxicity.

Although difficult to conceive, the creation of a very large number of ESC lines might be one way to obtain a diversity of cells that could



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