Tissue Transplantation

“Transplantation is the transfer (engraftment) of human cells, tissues or organs from a donor to a recipient with the aim of restoring function(s) in the body.”

Transplant:

“Also called graft, in medicine, a section of tissue or a complete organ that is removed from its original natural site and transferred to a new position in the same person or in a separate individual.

Types Of Transplants:

Autograft: Auto-grafts are the transplant of tissue to the same person. Sometimes this is done with surplus tissue can regenerate or tissues more desperately needed elsewhere (examples include skin grafts, vein extraction etc.). In a rotationplasty , a distal joint is used to replace a more proximal one; typically a foot or ankle joint is used to replace a knee joint. The patient’s foot is severed and reversed, the knee removed, and the tibia joined with the femur.
Allograft and allotransplantation: An allograft is a transplant of an organ or tissue between two genetically non-identical members of the same species. Most human tissue and organ transplants are allografts. Due to the genetic difference between the organ and the recipient, the recipient’s immune system will identify the organ as foreign and attempt to destroy it, causing transplant rejection.
Isograft: A subset of allografts in which organs or tissues are transplanted from a donor to a genetically identical recipient (such as an identical twin). Isografts are differentiated from other types of transplants because while they are anatomically identical to allografts, they do not trigger an immune response.
Xenograft and Xenotransplantation: A transplant of organs or tissue from one species to another. An example is porcine heart valve transplant, which is quite common and successful. However, xenotransplantion is often an extremely dangerous type of transplant because of the increased risk of non-compatibility, rejection, and disease carried in the tissue.
Split Transplants: Sometimes a deceased-donor organ, usually a liver, may be divided between two recipients, especially an adult and a child. This is not usually a preferred option because the transplantation of a whole organ is more successful.
Domino transplants: In patients with cystic fibrosis, where both lungs need to be replaced, it is a technically easier operation with a higher rate of success to replace both the heart and lungs of the recipient with those of the donor. As the recipient’s original heart is usually healthy, it can then be transplanted into a second recipient in need of a heart transplant. Another example of this situation occurs with a special form of liver transplant in which the recipient suffers from familial amyloidotic polyneuropathy, a disease where the liver slowly produces a protein that damages other organs. The recipient’s liver can then be transplanted into an older patient for whom the effects of the disease will not necessarily contribute significantly to mortality. 7-ABO-incompatible transplants: Because very young children (generally under 12 months, but often as old as 24 months) do not have a well-developed immune system,] it is possible for them to receive organs from otherwise incompatible donors. This is known as ABO-incompatible (ABOi) transplantation. Graft survival and patient mortality is approximately the same between ABOi and ABO-compatible (ABOc) recipients. While focus has been on infant heart transplants, the principles generally apply to other forms of solid organ transplantation. Limited success has been achieved in ABO-incompatible heart transplants in adults,though this requires that the adult recipients have low levels of anti-A or anti-B antibodies.Kidney transplantation is more successful, with similar long-term graft survival rates to ABOc transplants.

Types Of Donor:

Living Donor: In living donors, the donor remains alive and donates a renewable tissue, cell, or fluid (e.g., blood, skin), or donates an organ or part of an organ in which the remaining organ can regenerate or take on the workload of the rest of the organ (primarily single kidney donation, partial donation of liver, lung lobe, small bowel). Regenerative medicine may one day allow for laboratory-grown organs, using patient’s own cells via stem cells, or healthy cells extracted from the failing organs
Deceased Donor: Deceased donors (formerly cadaveric) are people who have been declared brain-dead and whose organs are kept viable by ventilators or other mechanical mechanisms until they can be excised for transplantation. There are two kinds of transplant:
Tissue transplants
Organ transplants

Tissue Transplants:

In this, tissues are transferred from donor to recipient , instead of transplanting whole organ. For example

Skin: Most skin grafting is with autografts; the special indication for skin allografts in severely burned patients has been mentioned. Skin allografts seem to be rejected more aggressively than any other tissue, and there are many experimental situations in which skin grafts between two inbred strains of animal fail, although kidney grafts between the same strains survive indefinitely. There can be no doubt that, if rejection could be predictably and safely overcome, there would suddenly be a whole new field of surgery. With autografts, the donor skin is limited to what the patient has available, and sometimes in extensive burn cases this becomes a matter of robbing Peter to pay Paul. If allografts were not rejected, skin from cadavers could be used for coverage of burned areas without the need for subsequent autografting, and many lives would be saved.
Full-Thickness Free-Skin Grafts: Full-thickness free-skin grafts are the maximum thickness that can survive without a blood supply, and they are therefore in some danger of failure to survive. These grafts produce good cosmetic appearances and are especially useful on the face. The main defect of a full-thickness free-skin graftis that, unless it is very small, the donor site from which it comes becomes a defect that needs to be closed in its own right and may itself need skin grafting.
Split Or Partial-Thickness Skin Grafts: Split, or partial-thickness, skin grafts are by far the most commonly used grafts in plastic surgery. Superficial slices of skin the thickness of tissue paper are cut with a hand or mechanical razor. The graft, which contains living cells, is so thin that it usually gains adequate nourishment directly from the raw surface to which it is applied, and the risk of failure to take (that is, to survive in the new location) is therefore much less than with full-thickness grafts. Another major advantage is that the donor site is not badly damaged. It is tender for only two or three weeks, and it resembles a superficial graze both in appearance and in the fact that healing takes place from the deep layer of the skin left behind. Split skin grafts can be taken quickly from large areas to cover big defects. They tend to have an abnormal shiny reddish appearance that is not as satisfactory cosmetically as the other types of skin graft.
Cornea: There are certain forms of blindness in which the eye is entirely normal apart from opacity of the front window, or cornea. The opacity may be the result of disease or injury, but, if the clouded cornea is removed and replaced by a corneal transplant, normal vision can result. Since cells of the cornea remain viable for some 12 hours after death, a cornea can be grafted if it is removed within that period. Cooling will slow the process of deterioration, although the sooner the section of cornea is transplanted the better. The graft bed to which a cornea is transplanted has no blood supply. Nourishment comes directly by diffusion from the tissues. Because most rejection factors are carried in the bloodstream, the lack of blood vessels permits most corneal allografts to survive indefinitely without rejection. Rejection can occur if, as sometimes happens, blood vessels grow into the graft.
Blood vessels: By far the most satisfactory blood-vessel transplant is an autograft, similar in principle to skin autografts. Blood-vessel grafts are frequently used to bypass arteries that have become blocked or dangerously narrowed by fatty deposits, a condition caused by degenerative atherosclerosis (hardening of the arteries). Such atherosclerotic deposits in the coronary and carotid arteries are responsible, respectively, for most heart attacks and strokes. If atherosclerosis affects the mainartery of the leg, the result is first pain in the calves and then gangrene of the foot, If dealt with early, the effects of the arterial blockage can often be overcome by removing a nonessential superficial vein from the leg, reversing it so that the valves will not obstruct blood flow, and then joining this graft to the affected artery above and below the block—thus bypassing the obstruction. Coronary-artery-bypass grafting has become one of the most common surgical operations in developed countries. Vein or arterial allografts are far less successful. In time the walls tend to degenerate, and the vessels either dilate, with the danger of bursting, or become obstructed.
Heart valves: Valvular diseases of the heart can be dangerous, since both a blocked valve and a valve that allows blood to leak backward create a strain on the heart that can lead to heart failure. If the valve is seriously damaged, it can be replaced with a xenograft valve or a manufactured mechanical valve. Neither is ideal. Xenograft valves have a normal central blood flow, but after a few years they may become rigid and cease to function. Plastic valves—usually of the ball-valve or trapdoor types—force blood to flow around the surface of the ball or trapdoor flap, and this tends to damage red blood cells and cause anemia. Synthetic heart valves require ongoing anticoagulation therapy.
Bone: When fractures fail to unite, autografts of bone can be extremely valuable in helping the bone to heal. Bone allografts can be used for similar purposes, but they are not as satisfactory, since the bone cells are either dead when grafted or are rejected. Thus, the graft is merely a structural scaffold that, although useful as such, cannot partake actively in healing.
Fascia: Fascia, sheets of strong connective tissue that surround muscle bundles, may be used as autografts to repair hernias. The principle of use is like that for skin.
Nerves: Nerves outside the brain and spinal cord can regenerate if damaged. If the delicate sheaths containing the nerves are cut, however, as must happen if a nerve is partially or completely severed, regeneration may not be possible. Even if regeneration occurs it is unlikely to be complete, since most nerves are mixed motor and sensory paths and there is no control ensuring that regenerating fibers take the correct path. Thus, there will always be some fibers that end in the wrong destination and are therefore unable to function. Defective nerve regeneration is the main reason why limb grafts usually are unsatisfactory. A mechanical artificial limb is likely to be of more value to the patient.
Blood: Blood transfusion has been one of the most important factors in the development of modern surgery. There are many lifesaving surgical procedures that are possible only because the blood loss inevitable in the operation can be made up by transfusion. Blood transfusion is of value in saving life following major injury, bleeding ulcers, childbirth, and many other conditions involving dangerous loss of blood. Purified blood components can be transfused to treat specific defects; for example, platelets are used to correct a low platelet count, and clotting factor VIII is given to counteract the clotting defect in classic hemophilia.
Bone marrow: Diseases, in which the bone marrow is defective, such as aplastic anemia, may be treated by marrow grafting. Some forms of leukemia can be cured by destroying the patient’s bone marrow—the site of the cancerous cells—with drugs and irradiation. Marrow grafting is then necessary to rescue the patient. There is a tendency for the patient to reject the allografted marrow, and there is an additional hazard because immune-system cells in a marrow graft can react against the patient’s tissues, causing serious and sometimes fatal graft-versushost disease. To avoid these complications, special immunosuppressive treatment is given. The use of monoclonal antibodies to selectively remove harmful lymphocytes from the donor marrow has produced encouraging results in preventing graft-versus-host disease.

Tissue Rejection:

Human beings possess complex defense mechanisms against bacteria, viruses, and other foreign materials that enter the body. These mechanisms, which collectively make up the immune system, cannot, unfortunately, differentiate between disease-causing microorganisms and the cells of a lifesaving transplant. Both are perceived as foreign, and both are subject to attack by the immune system. This immune reaction leads to rejection, the greatest problem in successful tissue and organ grafting.

Immune Responses:

In order to understand why rejection occurs and how it may be prevented, it is necessary to know something of the operations of the immune system. The key cells of the immune system are the white blood cells known as lymphocytes. These are of two basic types:

T lymphocytes
B lymphocytes.

These cells have the capacity to distinguish “self” substances from such “nonself” substances as microorganisms and foreign tissue cells. Substances that provoke an immune reaction are recognized by the presence of certain molecules, called antigens, on their surface. T lymphocytes are responsible for what is called cell-mediated immunity, so named because the T cells themselves latch onto the antigens of the invader and then initiate reactions that lead to the destruction of the non-self-matter. B lymphocytes, on the other hand, do not directly attack invaders. Rather, they produce antibodies, proteins that are capable of initiating reactions that weaken or destroy the foreign substance. The overall immune reaction is exceedingly complex, with T lymphocytes, B lymphocytes, macrophages (scavenger cells), and various circulating chemicals waging a coordinated assault on the invader. Transplant rejection is generally caused by cell-mediated responses. The process usually occurs over days or months, as the T lymphocytes stimulate the infiltration and destruction of the graft. The transplant may be saved if the cell-mediated reactions can be suppressed. Antibody attack of transplanted tissues is most apparent when the recipient has preexisting antibodies against the antigens of the donor. This situation can arise if the recipient has been previously exposed to foreign antigens as the result of pregnancy (during which the mother is exposed to fetal antigens contributed by the father), blood transfusions, or prior transplants. Unlike a cellmediated reaction, antibody-mediated rejection is rapid, occurring within minutes or hours, and cannot be reversed.

Selection of Donor And Tissue Matching OR Typing Procedures: (Determining the Presence Of Potentially Reactive Antigens)

The factors that provoke graft rejection are called transplantation or histocompatibility, antigens. If donor and recipient have the same antigens, as do identical twins, there can be no rejection. All cells in the body have transplantation antigens except the red blood cells, which carry their own system of blood-group (ABO) antigens.

ABO typing: Basic ABO compatibility depends on the presence or absence of antigens on donor RBCs and the presence or absence of specific antibodies to these antigens in the recipient’s serum. Anti-ABO antibodies are of the IgM classification and cause agglutination, complement fixation, and hemolysis. If an ABO-incompatible graft is transplanted, hyperacute rejection will occur (the possible exception being Page 9 a liver graft). In kidney transplantation, preformed circulating cytotoxic antibodies in the recipient react with ABO isoagglutinins produced by the graft, and the graft quickly turns dark and soft as a result of diffuse thrombosis of the microvasculature.

Rho (D) antigens: Rho antigens are not expressed on endothelial tissue and therefore play no apparent role in graft rejection or survival. In other words, an organ from a donor with ABO type B positive can be safely transplanted into a recipient with ABO type B negative.

HLA typing (microlymphocytotoxicity testing): The main human transplantation antigens—called the major histocompatibility complex, or the HLA (human leukocyte antigens) system—are governed by genes on the sixth chromosome. HLA antigens are divided into two groups:

Class I antigens, which are the target of an effector rejection response.
Class II antigens, which are the initiators of the rejection reaction.

Class II antigens are not found in all tissues, although class I antigens are. Certain macrophage like tissue cells—called dendritic cells because of their finger-like processes—have a high expression of class II antigens. There has been much interest in trying to remove such cells from an organ graft, so that the rejection reaction will not be initiated. There has been some experimental success with this approach, although it has not yet been applied clinically. Tissue typing involves the identification of an individual’s HLA antigens. Lymphocytes are used for typing. It is important also that the red blood cells be grouped, since red-cell-group antigens are present in other tissues and can cause graft rejection. Although transplantation antigens are numerous and complicated, the principles of tissue typing are the same as for red-cell grouping. The lymphocytes being typed are mixed with a typing reagent, a serum that contains antibodies to certain HLA antigens. If the lymphocytes carry HLA antigens for which the reagent has antibodies, the lymphocytes agglutinate (clump together) or die. Typing serums are obtained from the blood of persons who have rejected grafts or have had multiple blood transfusions or multiple pregnancies; as previously stated, such persons may develop antibodies to transplantation antigens. If the lymphocytes of both the recipient and the potential donor are killed by a given serum, then, as far as that typing serum is concerned, the individuals have antigens in common. If neither donor nor recipient lymphocytes are affected, then donor and recipient lack antigens in common. If the donor lymphocytes are killed but not those of the recipient, then an antigen is present in the donor and is missing from the recipient. Thus, by testing their lymphocytes against a spectrum of typing sera, it is possible to determine how closely the recipient and donor match in HLA antigens. As a final precaution before grafting, a direct cross-match is performed between the recipient’s serum and donor lymphocytes. A positive cross-match usually contraindicates the donor–recipient transplant under consideration. There is now considerable knowledge concerning the inheritance of transplantation antigens, but, even so, tissue typing is not sufficiently advanced to give an accurate prediction of the outcome of a graft in an individual case, particularly when the donor and recipient are not related to one another. In accordance with Mendelian laws of inheritance, a person obtains one of a pair of chromosomes from each parent. Therefore, a parent-to-child transplant will always be half-matched for transplantation antigens. Siblings have a one-in-four chance of a complete match of the HLA antigens, a one-in-four chance of no match, and a one-in-two chance of a half-match.

References:

Waqas Khan

BSc (Hon) Zoology – GCU Lahore

MPhil – Wildlife Ecology – Quaid e azam university , Islamabad

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Tissue Transplantation

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