The science of transferring a graft from one part of the body to another or from one individual to another. The graft may consist of an organ, tissue, or cells. If donor and recipient are the same individual, the graft is autologous. If donor and recipient are genetically identical (monozygotic), it is syngeneic. If donor and recipient are any other same-species individuals, the graft is allogeneic. If the donor and recipient are of different species, it is called xenogeneic.
In theory, virtually any tissue or organ can be transplanted. The principal technical problems have been defined and, in general, overcome. Remaining major problems concern the safety of methods used to prevent graft rejection and the procurement of adequate numbers of donor organs.
Living volunteers can donate one of a pair of organs, such as a kidney, only one of which is necessary for normal life. Volunteer donors may also be employed for large unpaired organs such as small bowel, liver, or pancreas, segments of which can be removed without impairment of function. Living donors can also provide tissues capable of regeneration; these include blood, bone marrow, and the superficial layers of the skin. In the case of a vital, unpaired organ, such as the heart, the use of cadaver donors is obligatory. In practice, with the exception of blood and bone marrow, the great majority of transplanted organs are cadaveric in origin, a necessity that presents difficult logistic problems.
Autografts are used for an increasing number of purposes. Skin autografts are important in the treatment of full-thickness skin loss due to extensive burns or other injuries. Provided that the grafts comprise only the superficial levels of the skin, the donor sites reepithelialize spontaneously within a week or two. The saphenous vein of the ankle is frequently transplanted to the heart to bypass coronary arteries obstructed by atherosclerosis. Autologous hematopoietic stem cell transplantation is sometimes used to restore blood cells to cancer patients who receive forms of chemotherapy that are lethal to their bone marrow.
The most serious problem restricting the use of allografts is immunological. Because cells in the donor graft express on their surface a number of genetically determined transplantation antigens that are not present in the recipient, allografts provoke a defensive reaction analogous to that evoked by pathogenic microorganisms. As a consequence, after a transient initial period of apparent well-being, graft function progressively deteriorates and the donor tissue is eventually destroyed. The host response, known as allograft rejection, involves a large number of immunological agents, including cytotoxic antibodies and effector lymphocytes of various types. There are a few special exemptions from rejection that apply to certain sites in the body or to certain types of graft. For example, the use of corneal allografts in restoring sight to individuals with corneal opacification succeeds because of the absence of blood vessels in the host tissue.
Successful transplantation of allografts such as kidneys and hearts currently requires suppressing the recipient's immune response to the graft without seriously impairing the immunological defense against infection. Treatment of individuals with so-called immunosuppressive drugs and other agents prevents allograft rejection for prolonged periods, if not indefinitely. Under cover of nonspecific immunosuppression, the recipient's immune system appears to undergo an adaptation to the presence of the graft, allowing the dosage of the drugs to be reduced. However, in almost all successfully transplanted individuals, drug therapy at some low dose is required indefinitely. See Immunosuppression
An individual's response against an allograft is directed against a large number of cell-surface transplantation antigens controlled by allelic genes at many different loci. However, in all species, one of these loci, the major histocompatibility complex (MHC), transcends all the other histocompatibility loci in terms of its genetic complexity and the strength of the antigenic response it controls. In humans, the MHC, known as the HLA (human leukocyte antigen) complex, is on the sixth chromosome; its principal loci are designated A, B, C, DR, and DQ. The allelic products of the HLA genes can be detected by serology, polymerase chain reaction technology, or microcytotoxicity assays. The ABO red cell antigens are also important because they are expressed on all tissues. See Blood groups, Histocompatibility
In kidney transplants between closely related family members, the degree of HLA antigen matching can be determined very precisely, and there is a very good correlation between the number of shared HLA antigens and the survival of the graft. With grafts from unrelated donors, HLA matching is more difficult and can delay transplantation, but it may be beneficial. HLA matching is not as clearly beneficial in the case of most other solid organ grafts, and no attempt is made to HLA-match heart, lung, liver, and pancreas grafts. With few exceptions, however, most donors and recipients are matched for the expression of ABO blood group antigens.
Bone marrow transplantation presents a unique problem in its requirements for HLA matching and for immunosuppression in advance of grafting. In addition to the possibility of rejection of the graft by the recipient, by virtue of immunologically competent cells still present in the recipient, bone marrow grafts can react against the transplantation antigens of their hosts. These are known as graft-versus-host reactions, and they can be fatal. See Immunology
The immunological events that lead to the rejection of xenografts are different from and less well understood than those responsible for allograft rejection. The small number of xenografts attempted to date have failed. In particular, xenografts are susceptible to hyperacute rejection by humans. This is due to the presence of certain glycoproteins in blood vessels of many species that are recognized by antibodies present in the blood of all humans.