Medical Transplantation

Article Outline

Introduction; Transplant Rejection; Types of Transplants; Other Organ and Tissue Sources; Ethical Issues; History

Introduction

Medical Transplantation, transfer of a living tissue or organ to an injured or ill person to restore health or reduce disability. Since the first successful organ transplant in 1954, surgeons have made great strides in their ability to implant organs in people who are seriously ill. At least 21 different organs—such as hearts, livers, and kidneys—and tissues—such as corneas and bone marrow—can now be successfully transplanted into patients who can then expect to survive for years or even decades. Each year, more than 25,000 internal organs are successfully implanted into patients in the United States and more than 1,700 organ transplants are performed in Canada. Improved surgical techniques are partly responsible for the success of organ transplants, but a more important factor is the development of drugs that can suppress the body’s rejection of the implanted organ without also leaving the patient highly susceptible to infections.

But this success also created a major problem: As the demand for organs grew, it soon outstripped the supply of donated organs. As of February 2006, more than 90,000 Americans were on a waiting list for organs or tissues and as of December 2004, more than 4,000 Canadians were also on a waiting list. Each year in the United States, more than 6,000 die before a donated organ can be found. In order to match the scarce supply of donated organs with critically ill patients, in 1984 the United States Congress passed the National Organ Transplant Act to regulate the transplant business. The United Network for Organ Sharing (UNOS) serves as the umbrella organization for organ procurement and transplantation centers around the nation.

When a physician determines that a patient requires a transplant, the patient’s medical information is sent to the closest transplant center. At the transplant center, candidates are evaluated and ranked according to medical criteria. The patient’s medical records are then sent to UNOS for inclusion on its computerized waiting list.

When a donated organ becomes available, it is offered to patients on a waiting list in the donor’s local area. A match is made if laboratory tests show that the recipient is compatible with the available organ, reducing the risk that the organ will be rejected, and if the patient is healthy enough and available to undergo major surgery immediately. If the highest-ranked patient on the list does not meet these criteria, the organ is offered to the next patient on the list. If no one locally can use the organ, it is offered regionally. If it cannot be used regionally, in rare cases the organ is offered to the highest-ranking patient elsewhere in the United States.

Transplant Rejection

Print this section

For medical transplantation to be successful, physicians must elude the combative efforts of the body’s complex immune system, which fights to protect the body from infections of all sorts. Central to the functioning of the immune system is its ability to distinguish between invading or foreign matter, which should be attacked, and matter that is a normal part of the body, which should not be attacked. This recognition system uses specific markers called histocompatibility antigens that are on the surface of all cells in an individual’s body. The immune system attacks anything that lacks these histocompatibility antigens or has antigens different from those found in the rest of the body, such as those found on invading viruses, bacteria, or other microorganisms. This recognition system causes the immune system to attack transplanted tissues that have different antigens because it has no way to distinguish between harmful and beneficial foreign matter.

There are over 200 different histocompatibility antigens, with each individual having a specific set of them. The odds that two unrelated people will have the same set of histocompatibility antigens are about one in 30,000. Transplant surgeons attempt to match histocompatibility antigens of the donor and the recipient as closely as possible in order to minimize rejection. In most cases, the match will not be exact, and the recipients must take drugs to suppress the immune response. The first drugs that were used were azathioprine and prednisone. But these drugs suppress the entire immune system, leaving the recipient vulnerable to infections and certain cancers. They also have toxic side effects.

A major breakthrough in immune suppression was the development of cyclosporine, a natural product derived from a fungus found in soil. Cyclosporine suppresses the part of the immune system involved in organ rejection with less severe impact on other parts of the immune system. A few years later, the drug tacrolimus (FK-506) was found to be even more effective for kidney, liver, heart, and lung transplants. However, patients who take these two drugs still face some increased risk of infection and cancer, and the drugs can cause kidney damage. Doctors often use a combination of immune-suppressing drugs to limit these side effects.

III

Types of Transplants

Print this section

Kidneys are the most common organs to be transplanted. Kidneys remove waste products from the blood stream. If they fail, often as a result of diabetes mellitus or cancer, a person can die from the buildup of these toxic materials. The waste products can be removed artificially through a process called kidney dialysis, but the patient must be hooked up to the dialysis machine two to three times each week for as long as 12 hours at a time. Kidney transplants free the recipient from dependence on dialysis. If the kidney is rejected, the patient must go back on dialysis or receive another transplant. The first successful transplant of any organ was performed in 1954, when American surgeon Joseph Murray successfully transplanted a kidney donated from the recipient’s twin brother.

In the United States, 15,207 kidney transplants were performed in 2005, of which 6,018 came from living donors. The one-year survival rate for kidney transplant patients is about 95 percent. Some kidney transplant patients have survived more than 25 years. Because people have two kidneys but need only one, a living relative often serves as a donor, retaining one kidney for his or her own use. About one-third of transplanted kidneys come from living relatives and about two-thirds are from someone who recently died.

Many patients whose kidney failure was caused by diabetes mellitus receive a pancreas transplant at the same time. The pancreas normally secretes insulin, a substance that helps the body use and store sugars. In some diabetics, the body’s immune system destroys insulin-secreting cells in the pancreas. In many cases, the disease can be controlled with shots of insulin. However, if the diabetic requires a kidney transplant, the surgeon will often transplant a pancreas at the same time. In 2005, there were 512 pancreas transplants and 835 simultaneous kidney and pancreas transplants performed in the United States. The one-year survival rate for pancreas transplant patients is about 95 percent.

Heart transplants are perhaps the most dramatic of all organ transplants because without a functioning heart, a patient cannot survive more than a few minutes. The heart is also more sensitive to a lack of blood than other organs, and can be preserved for only a few hours without damage. The first successful heart transplant was conducted in December 1967 by South African surgeon Christiaan Barnard. It was not until cyclosporine was approved for clinical use in the United States in 1983 that heart transplants gained widespread use. Most patients are able to resume a normal life about six months after surgery, and about 88 percent of them survive the first year. In 2005, about 2,000 patients received heart transplants in the United States.

Liver failure caused by cirrhosis, cancer, or hepatitis can be fatal. The liver is the only internal organ with the capacity to regenerate. This capacity provides the surgeon additional flexibility in treating liver damage. For instance, if the damage is not very severe, a temporary transplant can take over the liver’s function while the patient’s own liver recovers. It is also possible to remove part of a liver from a living donor and transplant it. After the surgery both the donor’s liver and the transplanted portion will grow to full size. In 2005, about 6,000 livers were transplanted in the United States. The one-year survival rate is about 87 percent.

Lung transplants are used to replace a single diseased lung, and sometimes both lungs. In some cases lung disease has damaged the heart, and these cases may benefit from a combined heart-lung transplantation. Successful lung transplants are hampered by the difficulty in preserving a lung from a person who has recently died so that it is still viable by the time a proper recipient is found. In 2005, there were 1,283 lung and 31 heart-lung transplants in the United States. The one-year survival rate for lung transplants is about 84 percent, while the one-year survival rate for heart-lung transplants is about 60 percent.

Other organ transplant surgeries are being developed and some are still in the experimental stage. In 1987, the first successful intestinal transplant was performed. The first successful small intestine transplant took place in 1991. In 2005, 164 intestines were transplanted in the United States to replace organs damaged by disease. The one-year survival rate for intestinal transplants is about 72 percent.

The most common tissue transplant is blood transfusion, commonly used to replace blood lost by a person in an accident or during surgery. Other tissues commonly transplanted include bone marrow, corneas, skin, bone, cartilage, tendons, and blood vessels.

Bone marrow is the living tissue found in the center of many large bones of the body. Special cells in the bone marrow, called stem cells, are the source of both red blood cells, the primary component of blood, and white blood cells, the workhorses of the immune system. Certain blood diseases, including leukemia and sickle-cell anemia, are the result of the stem cells in the bone marrow producing faulty blood cells. In some cases, these diseases can be treated by destroying all of the patient’s bone marrow and replacing it with new donor bone marrow that does not produce the faulty blood cells. Bone marrow transplants are also used in fighting breast and other cancers because intensive radiation or chemotherapy used to cure the cancer also kills the patient’s bone marrow, which must then be replaced with a transplant.

Bone marrow transplants require a closer matching of donor and recipient than is the case with other types of transplants. If the match is not good enough, the recipient’s body may reject the bone marrow or the white blood cells generated by the donor marrow can attack the recipient’s body, a phenomenon known as graft-versus-host disease.

About 30 percent of patients who require a bone marrow transplant have a close family member who is suitably matched. The rest must find a suitable donor. In the United States, the federal government has established the National Marrow Donor Program registry, which currently lists more than 5.5 million potential donors. More than 2,500 bone marrow transplants occur every year in the United States from marrow donated from unrelated people. Success rates for bone marrow transplants vary depending on the type and stage of disease and the age and condition of the patient.

The cornea is the transparent front covering of the eye and is necessary for vision. Cornea transplants replace corneas that have become cloudy, swollen, or painful, usually as a long-term complication from cataract surgery. Corneas can also become scarred after an injury or require replacement because of birth defects. Cornea transplants are very successful, with a success rate of more than 90 percent if the cornea is placed on the eye in such a manner that blood vessels do not come into contact with it. Without blood vessels, the body cannot send immune cells to attack the cornea. About 46,000 cornea transplants are performed every year in the United States. Eye surgeons can also transplant scleral tissue, the fibrous tissue that forms the white of the eye. Sclera transplants are used to treat glaucoma patients and those requiring reconstructive eye surgeries.

Skin was the first tissue transplanted, and researchers used skin transplants in the late 1950s and early 1960s to decipher the immune system response to transplants. Most skin transplants are so-called autografts, in which skin is taken from one site on the recipient’s body and grafted onto an injured site, thus avoiding the problems with rejection. However, in cases where the amount of skin needed is greater than the recipient can provide, such as in burn victims with extensive burns, skin from donors is used. Donated skin is useful, even if not properly matched, since it provides temporary protection from infection while new skin grows. By the time the graft is rejected, new skin is present.

In 2005 French surgeons performed the world’s first partial face transplant on Isabelle Dinoire. After collapsing at home, Dinoire was disfigured by her dog, who apparently attempted to revive her. Dinoire lost her lips and chin and much of her nose in the mauling, exposing her teeth and lower jawbone and tearing her facial muscles. Once a suitable match was available, surgeons grafted the donor’s lips, chin, and nose to Dinoire’s injured face.

Other Organ and Tissue Sources

Print this section

In addition to organs donated from humans, researchers are exploring the use of partially or wholly artificial organs manufactured in the laboratory. The use of organs from other species of mammals, a technique called xenotransplantation, was researched in the 1990s but was largely abandoned by the early 21st century. Beginning in the 1990s, scientists were also looking at regenerating organs and tissues in the laboratory by using a patient’s own cells and then transplanting the regenerated organs into the patient. The first successful transplants of a regenerated organ—bladders that were regenerated and transplanted in seven patients—were reported in April 2006. Because the organs derived from the patients’ own cells, rejection by the immune system was not a problem.

Windows Live® Search Results

Medical Transplantation

Introduction

Transplant Rejection

Types of Transplants

Other Organ and Tissue Sources