embryonic tissues into discrete layers. It was unexpected that a component of blood could cross over a developmental separation to form a tissue type that ordinarily has a completely different embryonic origin (Lagasse et al., 2000). The findings noted above and other reports of cardiac and muscle tissue formation after bone marrow transplantation in mice (Bittner et al., 1999; Orlic et al., 2001) and of the development of neuron-like cells from bone marrow (Brazelton et al., 2000; Mezey, et al., 2000) have raised expectations that HSCs will eventually be shown to be able to give rise to multiple cell types from all three germ layers. One study has, in fact, demonstrated that a single HSC transplanted into an irradiated mouse generated not only blood components (from the mesoderm layer of the embryo), but also epithelial cells in the lungs, gut, (endoderm layer) and skin (ectoderm layer) (Krause et al., 2001). If HSCs are truly multipotent, their potential for life-saving regenerative therapies may be considerably expanded in the future.
The full potential of bone marrow transplantation to restore a healthy blood system in every needy patient is currently limited by the unavailability of HSCs in the quantity and purity that are crucial for successful transplantation. Because of their relative rarity (one in every 10,000 bone marrow cells) and the difficulty of separating them from other components of the blood, so-called bone marrow stem cell transplants are generally impure (NIH, 2001). The significance of such impurity is great. All cells of the body express on their surface a set of molecules called histocompatibility (i.e. tissue compatibility) antigens. If a patient receives a transplant of HSC cells from a donor that has histocompatibility antigens different from his own, the patient’s body will recognize and react to the cells as foreign. To increase the likelihood that histocompatibility antigens will match, it is preferred that donors be a related sibling of the transplant recipient. Even if their histocompatibility antigens do match, however, HSC transplants can be contaminated by T cells from the donor’s immune system.
That contamination can cause the recipient’s body to reject the material or can produce an immune reaction in which the T cells of the transplant attack the tissues of the recipient’s body, leading to a poten-