Grafts and grafting

Anatomy or system affected: All

Definition: The transplantation of tissue from one part of the body to another or from one individual to another to treat disease or injury; such surgery requires careful genetic matching to avoid a harmful immune response

Indications and Procedures

In medicine, a graft is a tissue region which is transferred from one part of the body to another body part (autograft) or from one individual to another individual (allograft). Grafts between individuals of differing species (xenografts) also are possible. The actual transfer of tissue is called a transplant. The identification and matching of appropriate tissue types and the surgical connection of the tissue constitute grafting.

Examples of autografts include the use of leg veins to reconstruct the coronary arteries during heart bypass surgery, skin transplants during reconstructive facial surgery, and thumb/big toe interposable transplants following the loss of a hand or foot digit. Examples of allografts include major organ transplants (including that of the heart, liver, and kidney), bone marrowtransplantation, and blood transfusions between two genetically matched individuals. Xenograft examples include the grafting of animal tissue, such as skin or stomach epithelia, to the equivalent body parts in humans.

Genetic matching of donor and recipient tissues in grafting and transplantation is critical to the success of the tissue graft. Thus, tissue compatibility, termed histocompatibility, is of primary importance for successful grafting. Autografts are the most successful grafts because they occur on the same individual, and consequently, there is no genetic difference between donor and recipient cells. As the genetic difference between donors and graft recipients increases, however, the probability decreases that a graft will be successful.

For example, grafts between identical twins are highly successful because the donor and recipient are genetically identical; hence, the situation is the same as an autograft. Grafts between siblings are likely to succeed. Allografts between people having distinct genetic differences, however, are less likely to succeed. Xenografts are extremely difficult except for basic mammalian tissues, such as epithelial tissue.

Histology is the study of tissues and their development within the human body. The four principal tissue types within the human body and within other mammalian species are epithelial tissue, which lines the inside and outside surfaces of organs throughout the body; connective tissue (such as cartilage, bone, fat, and blood), which provides structure or transport throughout the body; nervous tissue, which conducts electrical impulses as information networks throughout the body; and muscular tissue, which provides contractility and movement for various body parts. All organs consist of a specific pattern of these four tissues: Epithelial tissue provides cover and protection, connective tissue provides support, nervous tissue provides information from the central control regions of the brain, and muscular tissue allows responses to localized change in the organ. In addition, the cells of tissues subspecialize for unique roles within the tissue of which they are a part. For example, nervous system cells may specialize to form receiving sensory neurons or transmitting motor neurons.

Regardless of tissue type, each of the thousand trillion cells in an individual possesses the same basic genes as the others, and therefore many of the same proteins are expressed throughout the body. All cells within an individual have proteins located within the lipid bilayers of their cell membranes. Several of these proteins are located on every single cell of the individual and thus serve as genetic identification markers for the individual’s immune system. These cell surface identification proteins are called histocompatibility proteins.

The histocompatibility proteins, of which there are many, are encoded by a battery of human genes called the major histocompatibility complex (MHC). These proteins ensure tissue compatibility for all cells in an individual with respect to that individual’s immune system. The cells of the immune system recognize the specific histocompatibility proteins of one’s own cells as “self” markers. Foreign cells, which are missing a few or many of the individual’s specific set of histocompatibility proteins, are recognized by the immune system as “nonself” and are attacked. This self-versus-nonself reaction is how the immune system distinguishes its own cells from any invading foreign cells and tissues. Therefore, the histocompatibility proteins play a critical role in the successful identification of one’s own cells and the destruction of infections, such as those caused by bacterial or fungal cells.

An immune response occurs when immune system cells called leukocytes (white blood cells) cannot locate the specific “self” histocompatibility proteins on a sampled cell. A type of leukocyte called a T lymphocyte will release a protein called immunoglobulin to immobilize the foreign “nonself” cell lacking the correct histocompatibility antigens (the proteins on the cell membranes). Immunoglobulins, also called antibodies, are proteins secreted by T lymphocytes to immobilize foreign antigens.

After the T lymphocyte antibodies have immobilized the antigens on the foreign cells, another type of leukocyte called a B lymphocyte produces antibodies that attack the foreign antigens. Furthermore, the B lymphocytes will multiply themselves, creating millions of copies to produce a clone army of B lymphocytes, all of which make the same antibodies targeted at the same foreign antigens. These specialized clones constitute a memory cell line, which will attack these antigens again if the organism is exposed to them in the future. This reaction is the basis of immunization.

Furthermore, after the T and B lymphocyte antibodies immobilize the foreign antigens, phagocytic leukocytes, such as neutrophils and macrophages, migrate to the region to ingest and completely destroy the foreign cells. This process will continue until either the foreign cells are vanquished or the immune system is exhausted.

The immune response just described may appear simple, but it is very complicated. In addition to the complex chemical identification of histocompatibility proteins on all an individual’s cells, the production of specific antibodies by T and B lymphocytes involves an extraordinary rearrangement of genes within these immune cells that is still poorly understood.

The immune response directly affects grafts and grafting. For transplants performed between two individuals, most tissues require a close genetic match between the donor and the recipient. They should be as closely related to each other as possible so that they share a common genetic heritage and, therefore, a high probability that their respective cells have most, if not all, of the same histocompatibility proteins. A close genetic relationship between the graft donor and recipient maximizes the chance that a graft will succeed and that an immune response against nonself tissues will not occur.

Uses and Complications

Grafts, grafting, and transplants between individuals are extremely important in the treatment of maiming or disfiguring accidents and life-threatening diseases. A huge demand exists for grafted tissue, not merely organ transplants, for use in a variety of medical conditions and procedures.

The most common and successful types of grafts are autografts from one part of an individual’s body to another part, or from one identical twin to her or his sibling. In autograft cases, there is a perfect match for the histocompatibility proteins on all the cells and tissues. Thus, an immune response will not occur unless the immune system is abnormal in some way, as with such autoimmune diseases as lupus erythematosus and rheumatoid arthritis.

An example of an autograft is the transfer of a vein from the leg to the heart in a patient suffering from coronary artery disease; the grafted vein serves as a replacement coronary artery, supplying blood, nutrients, and oxygen to the heart muscle. Another type of autograft is the transfer of skin from the abdomen or pelvic region to the face as part of reconstructive plastic surgery. A severed thumb can be replaced by the big toe, its equivalent digit on the foot.

Allografts, those between different individuals, can be successful if there is careful genetic matching between the donor and recipient tissues. Because of the specificity of matching for certain tissue and cell types, donor-recipient matching may mean an average of any two people out of a thousand or, with more critical tissue lines, such as stem cells, two people out of ten million. Often, siblings will serve as tissue donors. Otherwise, the lengthy process of finding possible tissue donors and determining their specific histocompatibility profiles must be conducted before the graft can take place between a recipient and a matched tissue donor.

Grafts are simple between generalized surface tissue, such as epithelial and connective tissues. Pig epithelial tissue has been used for skin and stomach tissue grafts on human recipients. Bone marrow transplants for aplastic anemia and leukemia patients, however, require more difficult histocompatibility matching. The use of fetal nervous tissue grafts into the brain tissue of Alzheimer’s disease patients has yielded promising results in regenerating brain tissue and slowing the acceleration of this debilitating disease, which generally strikes older adults.

Grafts are useful for tissue lines lacking totipotence, the ability to regenerate damaged or dead cells. The example cited above of fetal tissue being used to treat Alzheimer’s disease is a clear illustration of such tissue-grafting applications. Mature brain tissue in adult humans cannot regenerate. Fetal tissue grafts, however, have facilitated the regenerative capacity of some brain tissue in these patients.

Likewise, stem cell lines, such as the red bone marrow of flat bones, where white blood cells (leukocytes) and red blood cells (erythrocytes) are manufactured, are important targets for tissue grafting. In leukemia, a patient’s bone marrow is rapidly producing malignant leukocytes. It is clear that the stem cell line producing these cells is aberrant in such patients. Consequently, a small graft of bone marrow tissue from a histocompatible donor’s bone marrow may lead to the establishment of a healthy stem cell line in the patient to stop the overproduction of aberrant cells.

In any grafting process, the donor tissue is surgically inserted and secured into the recipient’s tissue site. There, the tissue, if the graft is successful, can grow and expand into the localized organ region to perform its correct function in the individual’s body. In the event that there is not a histocompatible match between the donor tissue within the recipient’s body, two possible rejection mechanisms can ensue. In host-versus-graft disease (HVGD), which is the most common type, the recipient’s immune system releases antibodies and eventually destroys the donor tissue. In graft-versus-host disease (GVHD), immune system cells transplanted with the donor tissue into the recipient migrate into the recipient’s tissues and attack the cells; the recipient will become ill and may die. The grafted tissue has rejected the entire body into which it has been transferred.

Perspective and Prospects

In 1990, the Nobel Prize in Physiology or Medicine was awarded to American medical researchers Joseph E. Murray of the Harvard Medical School and E. Donnall Thomas of Seattle’s Fred Hutchinson Cancer Research Center. These two scientists were pioneers in the use of grafts, grafting, and tissue transplants to save people’s lives. Murray performed the first successful kidney transplant, between two identical twins, in 1954. Murray teamed with Thomas at Harvard to study methods for preventing host-versus-graft rejections. During the 1960s at the University of Washington, Thomas developed the technique of destroying a potential bone marrow recipient’s immune system using radiation, followed by the grafting of donor bone marrow tissue into the patient, thereby increasing the chances that the transplant will succeed before the patient’s immune system can become active again. Both scientists also made important discoveries concerning the major histocompatibility proteins.

Grafts and grafting play a vital role in medicine. Grafts can save the lives of people with such diseases as leukemia, anemia, and cancer and can be useful in reconstructing damaged organs and skin, especially for burn victims. In the twenty-first century, many developments, such as the artificial graft material StrataGraft, continue to emerge, although much research is needed to understand histocompatibility and to reduce the chance of tissue rejection.

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