Although recent advances in immunosuppressive therapies have enhanced the survival of transplants, acute rejection still occurs in a large number of recipients. Moreover, current immunosuppressive therapies carry with them some serious side effects, such as infection, drug toxicity, and undesirable metabolic effects. Although the induction of specific tolerance is the ultimate goal in transplant medicine, the precise mechanism by which tolerance occurs is not yet well understood.

Recent gene expression studies on a variety of cardiac diseases, for example, have provided new insights into the biological mechanisms of these diseases (Yang et al., 2000), yet the molecular mechanism by which immunological tolerance occurs in cardiac transplants is still largely unknown. Matsui et al . (2003), used GeneChip® Murine Genome U74Av2 Set arrays to investigate the global gene expression analysis in tolerizing murine cardiac allografts—heart transplants that are from the same species but of a different genetic makeup—and found that immunologic tolerance can be induced and maintained even when there is evidence of a marked pro-inflammatory gene expression in vivo. Moreover, this group of researchers was able to identify specific genes that were upregulated in the tolerizing cardiac allografts when compared to the rejecting grafts. Works like this one comprise one of the first steps in establishing the mechanism by which transplants are tolerated and hold the promise of transplant medicine, that is, to be able to share cells and organs without the repercussions such as organ failure, transplant rejection and opportunistic infections.

In addition to organ transplants, cell-based transplants such as hematopoietic stem cells (HSC), are often used to support high-dose chemotherapy for a variety of malignancies, including multiple myeloma (see below). Currently, there are 3 different sources of HSC: bone marrow, umbilical cord blood, and mobilized peripheral blood. The HSC that arise form these alternate sources have different repopulation characteristics and functional characteristics. Key in understanding the clinical use and consequences of alternate sources of stem cells is the knowledge of the molecular basis of the normal and aberrant hematopoiesis within different stem cell populations. In a study conducted in the Netherlands (Ng et al. 2004), gene expression profiling was accomplished on stem cells from the different sources. These experiments allowed the molecular characterization of HSC and a better understanding of the clinical utility among the different HSC sources.

Graft versus host disease (GVHD) is a serious complication following HSC transplantation. Acute GVHD occurs within 100 days of the transplant, and has serious clinical consequences such as enteritis, dermatitis, and can be fatal. Chronic GVHD develops after the first 100 days and has a severe effect on the skin. For this reason, Sugerman et al. (2004) studied the kinetics of gene expression in a murine model of GVHD. By isolating the RNA of affected mice at different time points, this group was able to obtain data that explains the development and cellular composition of GVHD, and by doing so was able to correlate the gene expression data with the histopathological evolution of the skin lesions.

GeneChip® technology is enabling transplant medicine scientists to gather genetic information that will ultimately afford us insight into how specific tolerance can be attained and manipulated in the clinical setting, without the current debilitating side effects.