transplantation, medical

transplantation, medical,

Types of Transplanted Tissues and Organs

Transplantation to replace such diseased or defective tissue as corneas and hearts necessarily requires a dead donor; paired organs such as kidneys, or large or regenerating organs or tissues such as skin, bowel, lung, liver, or blood, can be donated by live donors (see blood transfusionblood transfusion,
transfer of blood from one person to another, or from one animal to another of the same species. Transfusions are performed to replace a substantial loss of blood and as supportive treatment in certain diseases and blood disorders.
..... Click the link for more information. ). Skin autografts, employing skin from the patient's own body, are used to replace lost skin; autograft transplants are also done with bowel, bone, cartilage and other connective tissue, and ovarian tissue. Replacement skin for autografts is now also grown in laboratories. Autograft bladders, blood vessels, nostrils, and vaginas have also been grown from a patient's cells using various methods and been successfully implanted. Bone marrow transplants can come either from a donor or from stored host bone marrow. Controversial fetal tissue implantsfetal tissue implant
or fetal cell therapy,
implantation of tissue from a fetus into a patient. In experimental procedures, fetal brain tissue has been implanted in the brains of patients with Parkinson's disease so that the fetal tissue will supply chemicals lacking
..... Click the link for more information.  have been used for some neurodegenerative diseases and experimentally for fetus-to-fetus transplants in certain genetic disorders. In addition to transplanted human tissues and organs, artificial parts ranging from heart valves to hip sockets are routinely implanted. See also heart, artificialheart, artificial,
external or surgically implanted mechanical device designed to replace a patient's diseased heart. The first one used on a human being, the Jarvik-7, was implanted (1982) in Barney Clark, who lived for 112 days; another patient, William Schroeder, lived 620
..... Click the link for more information. .

Immunological Rejection of Transplanted Tissue

In transplanting complex organs (but not small tissue grafts), the larger blood vessels of the organ are surgically connected to those of the recipient. Connective tissue cells gradually link together the graft and host tissue. The main obstacle to successful transplantation is the rejection of foreign tissue by the host (see immunityimmunity,
ability of an organism to resist disease by identifying and destroying foreign substances or organisms. Although all animals have some immune capabilities, little is known about nonmammalian immunity.
..... Click the link for more information. ). Transplanted tissue from another individual (i.e., homograft, or allograft, tissue) contains antigens that stimulate an immune response from the host's lymphocytes. Homograft tissue is normally destroyed within a few weeks; the rejection mechanism is similar to that by which the body resists infection. The greater the number of foreign antigens on the donor organ, the more rapid and severe the rejection reactions.

Implantation of tissues grown from a patient's own cells (autograft transplants) will not provoke an immune reaction, which is one of the main reasons why the growing of tissues and organs in bioreactors for implantation is of interest to researchers. Organs donated from one identical twin to another are usually viable because such organs are antigenically identical, but even organs transplanted between individuals who are fairly closely matched antigenically, such as siblings, have a good chance of being rejected. An antigenic typing system based on human lymphocyte antigens (HLA typing), pioneered by Jean DaussetDausset, Jean
, 1916–2009, French immunologist. A physician specializing in blood diseases, he was the laboratory director of the National Blood Transfusion Center (1946–63) and a professor at the Univ. of Paris (1958–77) and the Collège de France.
..... Click the link for more information.  in Paris and Rose Payne at Stanford, has made it possible to identify histocompatibility and minimize rejection.

Today, most recipients of transplants are maintained on immunosuppressive drugsimmunosuppressive drug,
any of a variety of substances used to prevent production of antibodies. They are commonly used to prevent rejection by a recipient's body of an organ transplanted from a donor.
..... Click the link for more information. . The side-effects of such antirejection drugs, which can themselves be life threatening, include increased risk of infection, cancer, diabetes, and other conditions. In time, however, many patients develop a tolerance to the implanted organs, and some can eventually be weaned off the drugs.

Researchers continue to study various ways to fool the immune system into accepting foreign tissues or to take advantage of the immune response. A new technique for nerve transplant begins with the patient taking immunosuppressive drugs, but after the patient's damaged nerves begin to grow and connect along the transplant, the drugs are discontinued and the immune system is allowed to destroy the transplanted nerve.

Noncellular tissues or tissues where the donor cells are not important to the graft (e.g., bone and cartilage) can usually be successfully transplanted without rejection. In these transplants the grafts provide nonliving structural support within which the recipient's living cells gradually become established. Corneal transplants have a high success rate largely because there are so few blood vessels in the cornea that corneal antigens may never enter the host's system to stimulate an immune reaction. Bone-marrow transplants effectively bring their own immune system with them, often rejecting the new host, instead of the other way around, in a reaction known as graft-versus-host disease.

Artificial organs, such as artificial bone, can be implanted successfully because such organs (prostheses) do not produce antigenic substances. Artificial joints made of stainless steel have been developed; newer implants have used nonrusting titanium joints with the midsection of bone substitute composed of lightweight polyethylene.

Organ transplants from animals to humans are subject to hyperacute rejection, and transplantation of tissues from animals has been attempted for almost a century without much success. Some progress has been made, however, in circumventing the immune reaction. In one experimental approach, the tissues and organs of transgenic pigs, genetically engineered animals that have had human genes inserted, are combined with newly developed immunosuppressive drugs. In a potential step toward a different approach to developing swine that could be used as a source of organs, researchers have cloned pigs in which a gene that causes rejection by the human immune system has been genetically disrupted. The endangered species status of chimpanzees, genetically closest animals to humans, has eliminated their use as donors. Although transplants from animals to humans, called xenotransplants, might benefit the thousands of patients waiting for human organs, the possibility that they could spread some unknown animal virus into the human population has caused concern and delayed research experimentation.

History

Human tissue grafting was first performed in 1870 by a Swiss surgeon, Jacques Reverdin. In 1912 the French surgeon Alexis CarrelCarrel, Alexis
, 1873–1944, American surgeon and experimental biologist, b. near Lyons, France, M.D. Univ. of Lyons, 1900. Coming to the United States in 1905, he joined the staff of the Rockefeller Institute in 1906 and served as a member from 1912 to 1939.
..... Click the link for more information.  developed methods of joining blood vessels that made the transplantation of organs feasible. He advanced this technique further and stimulated the use of transplantation in experimental biology. He also developed fluids and the means of circulating them so that transplanted tissues could be kept alive outside a living body in artificial media. Theoretical work by Jean DaussetDausset, Jean
, 1916–2009, French immunologist. A physician specializing in blood diseases, he was the laboratory director of the National Blood Transfusion Center (1946–63) and a professor at the Univ. of Paris (1958–77) and the Collège de France.
..... Click the link for more information. , George Davis SnellSnell, George Davis,
1903–96, American immunologist, b. Bradford, Mass., Ph.D. Harvard, 1930. He was associated with the Jackson Laboratory in Bar Harbor, Maine from 1935 to 1973.
..... Click the link for more information.  and Baruj BenacerrafBenacerraf, Baruj
, 1920–2011, American immunologist, b. Caracas, Venezuela, grad. Columbia (B.S., 1942), Medical College of Virginia (M.D., 1945). Raised in Paris, his Sephardic Jewish family fled the Nazis and came to the United States at the outset of World War II; he
..... Click the link for more information.  on the genetic basis of histocompatibility paved the way for practical applications. In the 1940s, Sir Peter Brian MedawarMedawar, Sir Peter Brian
, 1915–87, British zoologist, b. Brazil. After graduate work at Oxford, he held research and teaching posts there. He was professor of zoology (1947–51) at the Univ.
..... Click the link for more information.  and Sir Macfarlane BurnetBurnet, Sir Macfarlane,
1899–1985, Australian virologist and physician. He was resident pathologist (1923–24) at the Royal Melbourne Hospital and a Beit fellow (1926–27) at the Lister Institute, London.
..... Click the link for more information.  described foreign tissue rejection and acquired immunological tolerance, opening the way for transplant operations. The first successful transplant of a human kidney (between identical twins) was made by Joseph E. MurrayMurray, Joseph Edward,
1919–2012, American surgeon, b. Milford, Mass., M.D. Harvard, 1943. Trained as a plastic surgeon, Murray became interested in organ transplants, performing the first human kidney transplant in 1954 between two men who were identical twins.
..... Click the link for more information.  in 1954. The first human heart transplant was performed by the South African surgeon Christiaan BarnardBarnard, Christiaan Neethling
, 1922–2001, South African surgeon. The son of a Dutch Reformed minister, Barnard studied medicine at the Univ. of Cape Town (M.B. 1946, M.D. 1953), then came to the United States in 1955 to improve his surgical technique under Owen H.
..... Click the link for more information.  in 1967; in 1968, Edward D. ThomasThomas, Edward Donnall,
1920–2012, American surgeon, b. Mart, Tex., M.D. Harvard, 1946. At the Univ. of Washington from 1963 (emeritus from 1990), Thomas performed (1969) the first successful bone marrow transplant between people who were not twins, using tissue
..... Click the link for more information.  performed the first successful bone-marrow transplant between people who were not twins. In the following decades liver, kidney, heart, pancreas, bone-marrow, small intestines, and multiple organ transplants became more and more routine.

As transplantation has become more common and more successful, the demand for organs has risen dramatically. The development of heart transplantation has produced an ongoing reexamination of the traditional biological and legal definitions of deathdeath,
cessation of all life (metabolic) processes. Death may involve the organism as a whole (somatic death) or may be confined to cells and tissues within the organism. Causes of death in human beings include injury, acute or chronic disease, and neoplasia (cancer).
..... Click the link for more information. , because obtaining a healthy organ for transplantation depends in large part on the earliest possible establishment of the donor's death. More than 2,000 heart transplants per year were being performed in the United States by the late 1990s, with thousands of patients waiting for available hearts. In all, more than 64,000 people were waiting to receive new organs, including hearts, kidneys, livers, lungs, and pancreases. Many people carry organ donor cards, which indicate their wish to donate if they are killed in an accident, and many states require hospitals to request donation from the families of eligible donors. A side effect of the demand for donated organs has been the increasing use of lung and liver tissue, as well as kidneys, from live donors. In younger children receiving a liver transplant due to acute liver failure, part of the child's liver may be left in the body in hope that the organ will recover and immunosuppressive drugs will no longer need to be taken.

In the late 1990s surprising successes were achieved in transplanting body parts other than organs. Surgeons in France and the United States were able to transplant hands that became partly functional without rejection crises. In 2005 a French surgical team achieved a partial face transplant, replacing damage areas (nose, lips, and chin) of a woman's face with skin and underlying tissues from a dead donor. A nearly total face transplant was performed in the United States three years later, and a total face transplant was performed in France the year after that. Although receiving less attention, successful transplants of knees, the trachea (windpipe), and the larynx (voice box) have also been achieved. Such operations, called nonvital transplants, have become possible owing to improved surgical techniques, monitoring of rejection, and drug therapy. Still largely experimental, they must be approved by ethics committees before being undertaken, especially as the risk of taking immunosuppressive drugs may outweigh the benefits of the operation.

Bibliography

See studies by R. Simmons et al. (1987) and M. Dowie (1988). See also L. Gutkind, Many Sleepless Nights: The World of Organ Transplantation (1988) and publications of the United Network for Organ Sharing.