Organ transplantation
Organ transplantation is a procedure that rapidly restores the function of a healthy organ to a person, usually another person, to compensate for the loss of function of the corresponding organ of the recipient as a result of a fatal disease.
Broadly speaking, organ transplantation includes cell and tissue transplants. If the donor who gives the organ and the recipient who receives the organ are the same person, the transplant is called autologous transplantation; although the donor and the recipient are not the same person, but the donor and the recipient (i.e., identical twins) have identical genetic qualities, the transplant is called homogeneous transplantation. Transplants between humans are called homozygous (allogeneic) transplants; transplants between animals of different species (e.g., transplanting a chimpanzee's heart or a baboon's liver into a human) are xenotransplants.
The commonly used organs for transplantation are kidney, heart, liver, pancreas and pancreatic islets, parathyroid glands, heart and lungs, bone marrow, cornea and so on. In developed countries, kidney transplantation has become the first choice of conventional treatment for benign end-stage renal disease (such as chronic glomerulonephritis, chronic pyelonephritis and other causes of chronic renal failure).
History of organ transplantation
Organ transplantation is active transplantation, and there are 3 technical hurdles that need to be broken in order to be successful.
One is that once the transplanted organ is implanted in the recipient's body, the blood vessels must be connected immediately to restore the blood supply for the delivery of nutrients, so that the cells can survive, which requires a set of surgical techniques that are different from those for suturing the general tissues, and this perfect method of vascular anastomosis operation was not created until 1903 by A. Carrell.
The second is that the isolated ischemic organs cut die in a short period of time (as little as a few minutes and as much as no more than an hour) at room temperature and cannot be used for transplantation. And it is impossible to accomplish transplantation in such a short period of time. Therefore, an attempt is made to keep the organ active, which is called organ preservation. The methods are cooling and continuous perfusion, because hypothermia reduces the cells' need for nutrients, thus prolonging the survival of the isolated organ, and perfusion supplies the necessary nutrients. It was not until the practical technique of hypothermic lavage was created by F.O. Belzer in 1967 and G.M. Collins in 1969 (both Americans), including a specially formulated lavage solution that safely preserved the activity of kidneys for transplantation for up to 24 hours. That's what it takes to win enough time for organ transplants.
Third, the medically used organ comes from another person. But the recipient, as a living being, has a natural ability and agency (the immune system) to recognize, control, destroy and annihilate foreign "non-self" tissues and organs that enter his or her body. This physiological immune process is manifested in clinical organ transplantation as rejection, leading to destruction of the transplanted organ and transplant failure. Transplanted organs, like other human cells, have two major antigens: ABO blood group and human leukocyte antigen (HLA), which determine the rejection of homologous transplants.There are only four ABO blood groups (O, A, B, AB), and it is not difficult to find donors and recipients with the same ABO blood group; however, HLA is exceptionally complex, and there are now seven loci that have been identified, namely HLA --A, B, C, D, DR, DQ, DP, ****148 antigens, the combination of which can exceed 2 million. Unless identical twins are born, it is virtually impossible to find donors and recipients with identical HLA. Therefore, rejection is bound to occur after homologous transplantation and must be reversed with powerful immunosuppressive measures. It was not until the 1960s that clinically effective immunosuppressive drugs were discovered: azathioprine (1961), prednisone (1963), antilymphocyte globulin (ALG, 1966), and cyclophosphamide (1971), which later enabled the long-term survival of transplanted organs.The first human kidney transplantation was carried out in 1962 by the American J.E. Murray (Nobel Prize Laureate for Physiology or Medicine, 1990). The first human kidney transplant in 1962 by J.E. Murray (Nobel Prize in Physiology or Medicine in 1990) achieved long-term survival, and organ transplantation became a reality as a medical treatment.
The first organ transplant
On December 3, 1989, the world's first successful liver, heart and kidney transplant. On this day, a transplant specialist from the University of Pittsburgh, USA, successfully performed the world's first multi-organ transplant of heart, liver and kidney on a patient after 21 and a half hours of hard work.
The woman, Cindy Martin, was 26 years old and was being treated for her second transplant. She had a heart transplant three years ago, but her body rejected the transplanted heart and she suffered from hepatitis and kidney dysfunction. Martin is in normal condition after the surgery.
Types of organ transplants
Organs to be transplanted that come in pairs (such as kidneys) can be taken from cadavers, or from a parent or sibling who voluntarily donates an organ, while single organs transplanted as a whole (such as hearts and livers) can only be taken from cadavers. Transplantation to the original anatomical site is called in situ transplantation, such as in situ liver transplantation, which requires the removal of the original diseased organ; while transplantation to other locations is called allograft or assisted transplantation, where the original organ can be removed or retained. If the transplanted organ loses its function, it can be removed and transplanted again, three times or even multiple times. Surgery that involves transplanting two organs at a time is called a combined transplant, such as a combined heart-lung transplant. Surgery that involves transplanting three or more organs at the same time is called multi-organ transplantation. When transplanting multiple abdominal organs (such as liver, stomach, pancreas, duodenum, upper jejunum), these organs only have a total vascularity, and only the arterial and venous trunks need to be anastomosed during transplantation, which is also known as "one-string organ group transplantation". The procedure, also known as a "cluster transplant," cannot be done with animal organs because the rejection that occurs after the operation is so violent that current medications cannot control it, and the transplanted organ does not survive for long periods of time.
The application of organ transplantation
After entering the 80's, due to the advancement of surgical techniques, improvement of preservation methods, development of high-speed transportation, establishment of transplantation centers, especially the application of new immunosuppressants with fewer side-effects and more powerful effects, such as cyclosporine A and the monoclonal antibody OKT3, the curative effect of organ transplantation and the judgement of death has been greatly improved, and the latest immunosuppressant that has been introduced is FK506. Nowadays, the commonly used organs for transplantation include kidney, heart, liver, pancreas and pancreatic islets, parathyroid glands, heart and lungs, bone marrow, cornea, etc.; those in the initial clinical or experimental stage include heart and lungs, lungs, small intestines, adrenals, thymus, testes, as well as hepatocytes, fetal hepatocytes, splenocytes infusion, etc. In advanced countries, renal transplantation has already been used. In advanced countries, kidney transplantation has become the first choice of conventional treatment for benign end-stage renal disease (e.g. chronic glomerulonephritis, chronic pyelonephritis and other causes of chronic renal failure), by the end of 1990, the world has carried out 234,559 cases (more than 5,000 times in China), the survivors of more than 10 years have appeared in batches, and many of them have resumed their work, married and given birth to children, as in the case of normal people. Heart and liver transplants were performed in 16,136 and 14,168 cases by 1990*** (3 and 58 cases respectively in China), with 1-year survival rates of 90% and 80% respectively, and the longest survival rate of 20 years, with work and life being very satisfactory. By the end of 1990, there had been 2836 cases of pancreas transplantation (8 cases in China), and there had been more than 8 years of functional survival, which was suitable for the treatment of type I diabetes mellitus. A string of organs group transplantation to 1990 has 21 cases, including the treatment of the upper abdomen liver, pancreas and other malignant tumors with abdominal lymphatic metastases in 15 cases, there are 9 cases of long-term survival. China has accumulated more experience and achieved better results in vascularized embryonic parathyroid transplantation, embryonic pancreatic islet transplantation, and vascularized allogeneic spleen transplantation and adrenal gland transplantation, which are rarely reported abroad. The transplantation of some parts, such as cornea, is more special. Probably due to the lack of blood vessel growth in this site, immunoreactive lymphocytes in the blood stream cannot contact the cornea, and this site becomes a preferential site for immunization. Therefore, corneal in situ transplantation is seldom rejected, and the result is very good, with a success rate of more than 95%; even if rejection occurs, it only manifests as corneal clouding, and the application of prednisolone is effective. Corneal transplantation has become a routine surgery, widely used in ophthalmology.
Tissue transplantation
This refers to the transplantation of various types of tissues, including skin, fat, fascia, tendon, dura mater, blood vessels, lymphatic vessels, cartilage and bone 2006 Guangxi organ transplantation forum. Among them, except for homologous skin transplantation is an active transplantation, the performance of which is the same as the characteristics of the above organ transplantation, all other types of tissue transplantation belong to another type, called inactive transplantation or structural transplantation. The function of the transplanted tissue does not depend on the cells within the transplanted tissue, but only on the mechanical structure provided by the grafted tissue: a supportive matrix and an anatomical network that allows similar cells from the recipient to settle there. Therefore, the activity of the cells within the graft tissue is not necessary for structural transplantation; in fact, these cells are inactivated. Fresh tissue can be used as a graft with viable cells, and rejection does not occur after transplantation; therefore, there is no need to apply immunosuppressive drugs.
Ethical issues in organ transplantation
The main ethical issue in organ transplantation is the circumstances under which the donor who provides the organ does so: is it voluntary or is there prior consent to donate the organ? Is it possible for the donor to maintain his/her quality of life without needing the organ? Or does the donor no longer need the organ provided? If the answers are all in the affirmative, organ transplantation can be considered ethical.
Many people in Western countries make wills in which they are willing to donate their organs free of charge to those who need it after their death. Western countries have more car accidents, and those who die in car accidents are generally in good health and have organs available for transplantation. There are also relatives who voluntarily donate a kidney to save the life of a relative. In France, it is stipulated that any person who has not expressed his refusal to donate his organs before his death shall be entitled to have his organs removed for transplantation after his death. Many foreign countries have begun to apply the concept of brain death, if the comatose patient's electroencephalogram is a straight line for many times, and does not belong to the taking of anesthetics, deep hypothermia, infants and young children and other cases, even if the artificial respirator, pressurizing drugs can still maintain the heartbeat of the blood pressure, but also can be confirmed as death, the organs can be provided for transplantation.
The U.S. has had applications to set up for-profit businesses to operate human organs for transplantation, but they were rejected by Congress. The reason is that once it becomes profitable to provide organs, some people may be tempted to make a profit by selling substandard organs, or even dissecting out people in desperate need of money and auctioning them off to people with money.
The technical requirements for organ transplants are high and the costs are staggering. The most common type of kidney transplant, for example, costs about $30,000 to $40,000 per case, not counting the lifelong immunosuppressant anti-rejection drugs that are taken after a successful operation. Liver transplantation costs several times more. When health resources are limited, the cost of organ transplant patients often crowds out the health resources available to others. This is an ethical issue that can not be ignored from the macro level of the Fourth Yangcheng Liver Transplantation Summit, but also a health economy and health policy issues. Foreign countries in the 1960s once widely carried out organ transplantation, and then reduced year by year, shrinking to a few centers for in-depth study. Of course, like corneal transplantation, skin transplantation and other costs are not large, storage requirements are not high and the efficacy of organ transplantation is worth promoting.
Organ transplantation is the process of placing a healthy organ, surgically or otherwise, into the body of a patient suffering from a serious disease and in critical condition, so that the organ can continue to function, thus giving the recipient of the donor a new lease on life.
Organ transplants had been a dream of mankind until the twentieth century, when the medical profession was still at a loss to treat patients with severe organ failure. Due to the limitations of the objective conditions, organ transplantation only remained in the stage of animal experiments. In the 1950s, doctors around the world began to conduct human trials, but the results of organ transplants were unsatisfactory due to the inability to control rejection after transplantation. This situation continued until Novartis invented the immunosuppressive drug, cyclosporine (Neosporin). The invention of cyclosporine led to a significant increase in post-transplant organ survival and a rapid development of organ transplantation, one of the major achievements of cutting-edge medicine in the twentieth century.
The organs that can receive organ transplants include:
Heart:Heart transplants are the only treatment for patients with heart failure due to various causes.
Lungs:Patients with end-stage benign lung disease, which cannot be cured by conventional medical treatment but are estimated to have a 1-3 year survival hope, may be considered for lung transplantation to improve their health.
Liver:Liver transplantation is the only option for patients with end-stage benign liver disease that cannot be treated with conventional medical procedures.
Kidney:When some diseases damage the kidneys and the kidneys cannot perform normal physiological functions, they will gradually develop into renal insufficiency and azotemia, and the end stage is uremia. The methods to save the life of uremia patients include dialysis and kidney transplantation.
Pancreas:Most pancreas transplants are done at the same time as kidney transplants, and are used primarily to treat advanced diabetes, type I diabetes, and post-pancreatectomy diabetes.
In addition to the above organs, there are also those with spleen and small intestine that can be cured by undergoing transplantation.
Contributions of Transplantation Medicine
Over the past half century, transplantation as an independent discipline has had its ups and downs to reach its present stage of clinical application, which has enabled thousands of terminally ill patients to regain their lives. Transplantation medicine deserves to be recognized as one of the medical miracles of this century and continues to expand and challenge other fields of medicine. The contributions of half a century of transplantation medicine to mankind are as follows:
1. Discovery of the major histocompatibility antigen system in humans and various commonly used experimental animals and clarification of the major histocompatibility complex (MHC) as a fundamental obstacle to transplantation therapy.
2. The development and refinement of surgical techniques for transplantation of various organs and the establishment and application of various microsurgical transplantation animal models.
3. The development and clinical application of immunosuppressants have enabled organ transplantation to become a stable and routine means of treatment China's organ transplantation science press conference.
4. Continuous and in-depth basic research from the cellular level to the subcellular level and up to the DNA level has laid the foundation for revealing the mechanism of rejection and seeking countermeasures for medication, which has brought the level of clinical diagnosis and treatment to a new height.
5. The understanding and challenges of novel diseases, such as graft-versus-host disease and xenosis, the relationship between microchimerism and autoimmune diseases proposed in this meeting.
6. The use of gene therapy in transplantation has the potential to herald the rise of cloning to develop antigen-free biological organ replacements. Whereas it was once suggested that the ultimate way forward for transplantation science lay in immune tolerance and xenotransplantation, there is now a tendency to think that bioengineered organs are more likely to kill two birds with one stone.
C.A. Vacanti's talk on histological engineering led into a reverie of the future. Applying polymer fibers as a substrate, a variety of cells are grown to form tissues with complex structures. The technique is proposed for ear or nose reconstruction. The research centers of the University of Cambridge and F. Bath in the United Kingdom have now mastered the genetic technology for controlling the development of frogs and are able to repeat the growth experiments of headless frogs, limbless frogs, or tailless tadpoles. Undoubtedly, this technology, like sheep cloning, will bring new hope to transplantation science on the one hand, and inspire waves of medical ethics debates on the other.
Organ transplants are categorized as follows:
1. Autologous transplants, in which the grafts are taken from the recipient's own body;
2. Homologous transplants, in which the grafts are taken from a donor whose genetics are identical or basically similar to the recipient's;
3. Homologous transplants, in which the grafts are taken from another body that is homologous but with genetic differences;
4. Xenotransplants, in which the grafts are taken from animals of different species. Graft taken from an animal of a different species.
Types of organ transplant rejection
I. Host versus graft reaction
The recipient's rejection of the donor's tissues and organs is known as host versus graft reaction (HVGR). According to the degree of compatibility of the graft with the host's tissues and the recipient's immune status, the transplantation rejection is manifested in three different types. Depending on the degree of graft-host tissue compatibility and the recipient's immune status, graft rejection is characterized by three different types.
(I) hyperacute rejection
Hyperacute rejection usually occurs 24 hours after transplantation. At present, it is believed that such rejection is mainly caused by ABO blood group antibodies or antibodies against Class I major histocompatibility antigens. These antibodies may be present in recipients who have received repeated blood transfusions, are pregnant, or have had a previous allogeneic transplant of some kind. In renal transplantation, such antibodies may bind to the vascular endothelial cells of the transplanted kidney, either through activation of complement with direct destruction of target cells or through multiple complement cleavage fragments produced during complement activation, leading to platelet aggregation, neutrophil infiltration and activation of the coagulation system, ultimately leading to severe local ischemia and graft necrosis. Once ultra-acute rejection occurs, without effective treatment, it will eventually lead to graft failure. Therefore, pre-transplantation ABO and HLa matching can be used to screen out unsuitable organ donors to prevent the occurrence of ultra-acute rejection.
(2) Acute rejection
Acute rejection is the most common type of rejection, which usually occurs within a few days to a few months after transplantation and proceeds rapidly. When acute rejection occurs in renal transplantation, it can be manifested as increased body temperature, local distension, decreased renal function, oliguria or even anuria, increased leukocytes in the urine, or the appearance of lymphocyturia and other clinical symptoms. Cellular immune response is the main cause of acute graft rejection, and CD4+T (TH1) cells and CD8+TC cells are the main effector cells. Even with pre-transplant HLA matching and immunosuppressive medications, acute rejection occurs in 30% to 50% of transplant recipients. Most acute rejection can be mitigated by increasing the dosage of immunosuppressive drugs.
(C) Chronic rejection
Chronic rejection (chronic rejection) usually occurs months to years after organ transplantation, and the main pathological feature is the proliferation of endothelial cells in the capillary beds of the transplanted organ, which narrows the lumen of the arteries and progressively fibrosis. Chronic immune inflammation is the main cause of these histopathologic changes. There is no ideal treatment for chronic rejection.
II. Graft versus host reaction
If the direction of the immune attack is from the graft against the host, i.e., the immune cells in the graft produce an immune response to the host's tissue antigens and cause tissue damage, then it is called a graft versus host reaction (GVHR). GVHR is mainly seen after bone marrow transplantation. In addition, GVHR can occur to varying degrees in spleen and thymus transplants, as well as in immunocompetent newborns receiving blood transfusions.
Acute GVHR usually occurs within 10-70 days after bone marrow transplantation. The occurrence of GVHR can be avoided if the T cells in the bone marrow are removed, suggesting that the T cells in the bone marrow are the main effector cells causing GVHR. However, clinical observations showed that the success rate of bone marrow implantation also decreased after removal of T cells in the bone marrow, and the relapse rate of leukemia, and the rate of viral and fungal infections also increased. This suggests that T cells in the bone marrow have a graft-versus-leukemia effect, which can overwhelm residual host immune cells and avoid host rejection of the graft; they can also play a role in fighting microbial infections when host immune reconstitution is incomplete. Therefore, selective de-targeting of T cells against host graft antigens and preservation of the remaining T cells not only avoids GVHR but also preserves their protective cellular immune function.
History of organ transplantation
Looking back at the history of medical development in the twentieth century, organ transplantation is undoubtedly a standing monument in the journey of mankind's conquest of diseases. Among them, liver transplantation is again the most difficult program, which requires not only a high-level surgical team, but also a vigorous and rich knowledge of related disciplines, in order to provide a chance of regeneration for patients with advanced liver disease.
In October 1977, the first human in situ liver transplantation was carried out in China
In July 2001, the first split liver transplantation was performed in China
In November 2004, the first combined transplantation of small intestine and liver was carried out in Shanghai
December 2004, the first combined transplantation of 7 organs was performed in China
In July 2005, the first case of using liver transplantation to successfully save a patient with acute fatty liver in pregnancy in China
In September 2005, Shanghai was the first to combine pancreaticoduodenectomy with liver transplantation
Regulations on Human Organ Transplantation