Donor-derived Chimerism in Recipients of Organ Transplants
The current issue of HEPATOLOGY features an article on "Cell Migration and Chimerism After Whole-organ Transplants" by Starzl et al. (1) at the University of Pittsburgh Health Science Center. This article, while overwhelming in its length and number of figures, brings together and adds to a flurry of recent reports in which this group has uncovered a new and potentially significant form of cell migration from organ grafts. Cells of donor (graft) origin widely populate the tissues of the recipient, resulting in a state of chimerism. This phenomenon was first noted after liver transplantation but also is apparent with grafts of intestine, lung, kidney and heart.
Cell migration and chimerism of the reverse sort (i.e., a movement from recipient to the graft) is not new. Recipient bone marrow-derived WBCs, particularly macrophages and dendritic cells, can repopulate the corresponding cellular compartments in any donor organ. What Starzl et al. have uncovered is a flux from donor to recipient. As they put it, all donor organs are to some extent "mini-marrows" and able to seed many recipient organs with donor-derived cells. The donorderived cells likely are white cells and may include specialized antigen-presenting dendritic cells (2).
We will summarize briefly the findings of Starzl et al., relating these to other instances of cell migration from donor to recipient. We will consider a possible mechanism for the phenomenon of long-term, donor-based chimerism and discuss the important consequences of chimerism that are proposed by the authors. There are three, which are as follows: (a) donor-derived cells influence the host's immune system and allow grafts to be accepted long term with reduced immunosuppression; (b) donor-derived cells can alleviate certain metabolic deficiencies such as type IV glycogen storage and Gaucher's diseases; and (c) implicitly, improved methods for treating transplant recipients and certain genetic deficiencies may be obtained by defining and enhancing donor-derived chimerism.
We suspect that most readers of HEPATOLOGY will agree that these three consequences of chimerism still lie in the realm of hypothesis.