362 
Monitoring Stem Cell Research 
of co-stimulatory molecules important for T cell activation. 
Transplantation of murine ES cells demonstrates long-term graft 
survival despite the fact that these cells do acquire HLA class II 
antigen expression after in vivo differentiation. Since they are able to 
accomplish long-term engraftment without the need for 
immunosuppression, their inability to induce an immune response is 
not likely to be the result of escaping immune surveillance, but rather 
due to their ability to colonize the recipient thymus and induce 
intrathymic deletion of alloreactive recipient T cells. 
Recently, a population of cells has been described in human adult 
bone marrow that has similar functional characteristics to embryonic 
stem cells in that they have high self-regenerating capability and 
capacity for differentiation into multiple cell types, including muscle, 
cartilage, fat, bone, and heart tissue. While such cells, termed adult 
mesenchymal stem cells (MSG), appear to have a more restricted 
self-renewal capacity and differentiation potential than ES cells, their 
functional characteristics may be sufficient for clinically meaningful 
tissue regeneration. A striking recent observation is that MSG can 
broadly inhibit T-cell proliferation and activation by various types of 
antigenic stimulation, including allogeneic stimuli. MSGs have been 
shown to inhibit both naive and memory T cell responses in a dose- 
dependent fashion and affect cell proliferation, cytotoxicity, and the 
number of interferon gamma (IFN-gamma)-producing T cells. MSGs 
appear to inhibit T cell activation through direct contact, and do not 
require other regulatory cellular populations. Similarly to ES cells, 
adult bone marrow-derived mesenchymal stem cells (MSGs) do not 
express HLA class II molecules, and only low levels of HLA class I 
molecules. Despite the fact that MSG can be induced to express 
surface HLA class II molecules by in vitro culture with cytokines 
such as interferon-gamma, their ability to inhibit T cell activation 
results in induction of T cell non-responsiveness to the MSG 
themselves, endowing them with potential survival advantages in 
the setting of transplantation. 
Tolerogenic Effects Of Stem Cell Transplantation 
Extending the approaches discussed above using donor-derived 
blood transfusions to induce a tolerogenic state to the subsequent 
organ, the most promising clinical strategy for tolerance induction at 
present is the use of donor-derived hematopoietic stem cells in 
conjunction with reduced myeloablative conditioning. The objective 
of this therapy is to achieve a state of so-called mixed chimerism, or 
the permanent co-existence of donor- and recipient-derived blood 
cells comprising all the different hematopoietic lineages in the same 
PRE -PUBLICATION VERSION 
