Can human organs be transplanted at will?

Organ transplantation is an operation to transplant a healthy organ into another person, usually to restore its function quickly and to compensate the recipient for losing the function of the corresponding organ due to a fatal disease.

Organ transplantation in a broad sense includes cell transplantation and tissue transplantation. If the donor who donates the organ and the recipient who receives the organ are the same person, this kind of transplantation is called autologous transplantation; Although the donor and recipient are not the same person, the donor and recipient (identical twins) have exactly the same genetic quality. This kind of transplantation is called allogeneic transplantation. Transplantation between people is called allogeneic transplantation; Transplantation between animals of different species (such as chimpanzee heart or baboon liver transplanted to humans) belongs to xenotransplantation.

Commonly used transplant organs are kidney, heart, liver, pancreas and islets, parathyroid gland, heart and lung, bone marrow, cornea and so on. In developed countries, renal transplantation has become the first choice for benign end-stage renal disease (such as chronic glomerulonephritis and chronic renal failure caused by chronic pyelonephritis).

History of organ transplantation

Organ transplantation is a living transplant. To succeed, there are three technical difficulties that need to be broken through.

First of all, once the transplanted organ is implanted in the recipient, the blood vessels must be connected immediately to restore the blood supply for transporting nutrients, so that the cells can survive. This requires a set of surgical techniques that are different from those used to suture general tissues, and this perfect vascular anastomosis method was not invented by A. Karel until 1903.

Secondly, the excised ischemic organ will die in a short time (at least a few minutes, most of which will not exceed 1 hour) at room temperature, so it cannot be used for transplantation. It is impossible to complete the transplant operation in such a short time. So try to keep the activity of organs, which is organ preservation. Methods include cooling and continuous perfusion, because low temperature can reduce the demand of cells for nutrients, thus prolonging the survival time of isolated organs, and perfusion can supply necessary nutrients. Until 1967, F.O. Beerse and G.M. Collins (both Americans) respectively invented practical cooling lavage technology, including a special lavage solution, which can safely preserve the activity of transplanted kidneys for 24 hours. Only in this way can we win enough time for organ transplantation.

Third, the organs used in medical treatment come from another person. The recipient, as a creature, has natural abilities and institutions (immune institutions), which can identify, control, destroy and destroy foreign "non-self" tissues and organs that enter its body. This physiological immune process is clinically manifested as rejection, which leads to the destruction of transplanted organs and the failure of transplantation. Just like other human cells, transplanted organs have two main antigens: ABO blood group and human leukocyte antigen (HLA), which determine the rejection of allograft. There are only four ABO blood types (O, A, B, AB), so it is not difficult to find blood donors and recipients with the same ABO blood type. However, HLA is extremely complex. At present, seven loci have been identified, namely HLA-A, B, C, D, DR, DQ, DP, *** 148 antigen, and their combination can exceed 2 million. Unless they are identical twins, it is practically impossible to find exactly the same HLA donor and recipient. Therefore, rejection after allogeneic transplantation is inevitable and must be reversed by strong immunosuppressive measures. Until the1960s, immunosuppressive drugs with clinical efficacy were discovered one after another: azathioprine (196 1), prednisone (1963), anti-lymphocyte globulin (ALG, 1966) and cyclophosphamide. 1962, American J.E. Murray (1990 Nobel Prize winner in Physiology or Medicine) performed human kidney transplantation for the first time, and achieved long-term survival. Organ transplantation has become a reality as a medical means.

The first organ transplant

1989 65438+February 3, the world's first liver-heart kidney transplant was successful. On this day, organ transplant experts from the University of Pittsburgh in the United States, after 2 1.5 hours of efforts, successfully performed the world's first multi-organ transplant operation for a patient.

Cindy Martin, a 26-year-old woman, is undergoing a second transplant. She received a heart transplant three years ago, but her body rejected the transplanted heart. She suffered from hepatitis and renal dysfunction. Martin is in normal condition after the operation.

kind

If the organ to be transplanted is a pair of organs (such as kidneys), it can be taken from a corpse or from parents or compatriots who voluntarily donate organs; A single organ (such as heart and liver) transplanted as a whole can only be taken from a corpse. Transplanting to the original anatomical site is called orthotopic transplantation, such as orthotopic liver transplantation. First, the original diseased organ should be removed. Transplanting to other locations is called heterotopic transplantation or auxiliary transplantation, and the original organ can be removed or preserved. If the transplanted organ loses its function, it can be taken out and transplanted again, three times or even many times. The operation of transplanting two organs at a time is called combined transplantation, such as combined heart-lung transplantation. The operation of transplanting more than three organs at the same time is called multiple organ transplantation. When transplanting multiple abdominal organs (such as liver, stomach, pancreas, duodenum and upper jejunum), these organs have only one common vascular pedicle, and only the arteriovenous trunks need to be anastomosed during transplantation. This operation is also called "serial organ transplantation". At present, animal organ transplantation is impossible, because the postoperative rejection is extremely fierce, the current drugs can not be controlled, and the transplanted organs can not survive for a long time.

App application

Since 1980s, the curative effect of organ transplantation has been greatly improved due to the progress of surgical techniques, the improvement of preservation methods, the development of high-speed transportation and the establishment of transplantation centers, especially the application of new immunosuppressants with little side effects and strong effects, such as cyclosporine A and monoclonal antibody OKT3. The latest immunosuppressant is FK506. Now commonly used transplant organs are kidney, heart, liver, pancreas and islets, parathyroid gland, heart and lung, bone marrow, cornea and so on. In the initial clinical use or experimental stage, heart, lung, small intestine, adrenal gland, thymus, testis, liver cells, fetal liver cells and spleen cells were infused. In developed countries, renal transplantation has become the first choice for benign end-stage renal disease (such as chronic glomerulonephritis and chronic renal failure caused by chronic pyelonephritis). By the end of 1990, 234,559 cases (more than 5,000 cases in China) had been implemented in the world, and a large number of people had survived for more than 10 years. Many people return to work, get married and have children as usual. From 1990 * * * to 16 136 and 1 4/68 cases (3 cases in China and 58 cases in China), the1year survival rates were above 90% and 80% respectively. By the end of 1990, there were 2836 cases of pancreas transplantation (8 cases in China), and those who survived for more than 8 years were suitable for treating type I diabetes. Since 1990, there have been 2 1 cases of continuous organ transplantation, among which 15 cases of upper abdominal liver, pancreas and other malignant tumors accompanied by abdominal lymph node metastasis, and 9 cases survived for a long time. China has accumulated a lot of experience in vascular embryo parathyroid transplantation, islet transplantation, spleen allograft and adrenal transplantation, and achieved good results. However, there are few reports about these transplants abroad. Some parts, such as corneal transplantation, are special. Perhaps it is because there is no blood vessel growth in this area, and the immunocompetent lymphocytes in the blood stream can't contact the cornea, so it becomes the immune priority area. Therefore, corneal orthotopic transplantation rarely produces rejection, and the effect is very good, with a success rate of over 95%. Even if rejection occurs, it is only manifested as corneal opacity, and prednisolone is effective. Corneal transplantation has become a routine operation and is widely used in ophthalmology.

tissue transplantation

Refers to the transplantation of skin, fat, fascia, tendon, dura mater, blood vessels, lymphatic vessels, cartilage, bone and other tissues. Among them, all kinds of tissue transplantation belong to another type, which is called inactive transplantation or structural transplantation, but the same skin transplantation belongs to active transplantation and has the same characteristics as the above organ transplantation. The function of the transplanted tissue does not depend on the cells in the transplanted tissue, but only on the mechanical structure provided by the transplanted plant tissue: supporting matrix and anatomical network, so that similar cells from the recipient can settle here. Therefore, when the structure is transplanted, the activity of cells in the transplanted tissue is unnecessary. In fact, these cells have lost their vitality. Fresh tissue can be used for transplantation, there are living cells, and rejection will not occur after transplantation, and immunosuppressive drugs are not needed.

Ethical issues in organ transplantation

The main ethical issue in organ transplantation is under what circumstances organ donors provide organs: voluntary consent or prior consent to donate organs? Can donors maintain their quality of life without this organ? Or do donors no longer need the organs provided? If all the answers are yes, organ transplantation can be considered ethical.

Many people in western countries have made wills and are willing to donate their organs to those in need for free after death. There are many car accidents in western countries. People who died in car accidents are generally healthy and organs can be transplanted. Some relatives volunteered to donate a kidney to save lives. France, on the other hand, stipulates that those who did not refuse to donate organs during their lifetime have the right to take out organs for transplantation after death. Many foreign countries have begun to apply the concept of brain death. If the EEG of coma patients is in a straight line for many times, and it does not belong to anesthesia, deep hypothermia, infants, etc. Even those who can maintain their heartbeat and blood pressure through artificial respiration machine and strengthening drugs can be confirmed as dead and their organs can be transplanted.

The United States applied to set up a for-profit enterprise to operate human organ transplantation, but it was rejected by Congress. Because once providing organs is profitable, it may induce some people to make profits, sell unqualified organs, and even dissect people who need money badly and auction them to the rich.

Organ transplantation requires high technology and the cost is staggering. Take the most common kidney transplantation as an example, each case costs about 30,000 ~ 40,000 yuan, not counting the anti-rejection immunosuppressants taken for life after successful operation. Liver transplantation costs several times more. In the case of limited health resources, the expenses of organ transplant patients often crowd out the health resources that others can enjoy. This is an ethical issue that can't be ignored macroscopically, and it is also a health economic and health policy issue. Organ transplantation was widely carried out abroad in the 1960s, and then decreased year by year, shrinking to several centers for in-depth research. Of course, corneal transplantation, skin transplantation and other organ transplants with low cost, low preservation requirements and positive results are worth popularizing.

Organ transplantation is to put a healthy organ into a dying patient with a serious disease through surgery or other methods, so that the organ can continue to function, thus giving the recipient a new life.

Organ transplantation was always a dream of human beings before the twentieth century. At the beginning of the twentieth century, the medical community was still at a loss to treat patients with severe organ failure. Due to various objective conditions, organ transplantation only stayed in the animal experiment stage at that time. In 1950s, doctors all over the world began to conduct human trials, but the effect of organ transplantation was not satisfactory because the rejection after transplantation could not be well controlled. This situation continued until Novartis invented the immunosuppressive drug-cyclosporine. The invention of cyclosporine greatly improved the survival rate after organ transplantation, and the cause of organ transplantation developed rapidly, which was one of the great achievements of cutting-edge medicine in the twentieth century.

Organs that can receive organ transplantation include:

Heart: Heart transplantation is the only treatment for patients with heart failure caused by various reasons.

Lung: Patients with advanced benign lung diseases can't be cured by traditional medical treatment, but it is estimated that there is still hope of survival for 1-3 years. We can consider lung transplantation to improve their physical condition.

Liver: Liver transplantation is the only method for patients with advanced benign liver disease, and these patients cannot be treated by traditional medical surgery.

Kidney: When some diseases damage the kidney and the kidney can't function normally, it will gradually develop into renal insufficiency. The disease of azotemia is uremia. Methods to save the lives of uremic patients include dialysis and kidney transplantation.

Pancreas: Pancreatic transplantation is mostly performed at the same time as renal transplantation, which is mainly used to treat advanced diabetes, type I diabetes and diabetes after pancreatectomy.

In addition to the above organs, patients with spleen and small intestine can be cured by transplantation.

Transplantation medicine's contribution

In the past half century, transplantation, as an independent subject, has gone through ups and downs and reached the stage of clinical application today, bringing thousands of terminally ill patients back to life. Transplantation medicine deserves to be one of the medical miracles of this century, and constantly expands and challenges other medical fields. Transplantation medicine's contribution to mankind for half a century is as follows:

1. The major histocompatibility antigen system of human beings and various commonly used experimental animals has been found, and the major histocompatibility complex (MHC) has been identified as the basic obstacle of transplantation treatment.

2. The development and perfection of various organ transplant surgical techniques, the establishment and application of various microsurgical transplant animal models.

3. The development and clinical application of immunosuppressants make organ transplantation a stable routine treatment.

4. In-depth basic research from cellular level to subcellular level to DNA level has laid a foundation for revealing the rejection mechanism and seeking drug countermeasures, which has brought the level of clinical diagnosis and treatment to a new height.

5. Understanding and challenges of new diseases, such as graft-versus-host disease and the relationship between xenotransplantation, microchimerism and autoimmune diseases.

6. The application of gene therapy in transplantation may indicate the rise of developing non-antigenic biological organ substitutes through cloning technology. Some people suggest that the ultimate way out of transplantation lies in immune tolerance and xenotransplantation, but now there is a tendency that bioengineered organs are more likely to kill two birds with one stone.

C.A.Vacanti's lecture on tissue engineering makes people daydream about the future. With polymer fiber as matrix, many kinds of cells can grow, thus forming tissues with renaturation structure. This technique is used for ear or nose reconstruction. The research center of Cambridge University and F.Bath has mastered the genetic technology to control frog development, and can repeat the growth experiment of headless frog, limbless frog or tailless tadpole. There is no doubt that this technology, like sheep cloning technology, will bring new hope to transplantation on the one hand, and arouse controversy on medical ethics on the other.

Types of organ transplant rejection

I. host anti-graft reaction

The rejection of donor tissues and organs by recipients is called host-versus-graft reaction (HVGR). According to the compatibility between the graft and the host tissue and the immune state of the recipient, the graft rejection mainly shows three different types.

(a) hyperacute rejection

Hyperacute rejection usually occurs 24 hours after transplantation. At present, it is believed that this rejection is mainly caused by ABO blood group antibodies or antibodies against major histocompatibility antigens of class I. This antibody may exist in recipients after repeated blood transfusion, pregnancy or previous allogeneic transplantation. In kidney transplantation, this antibody can bind to vascular endothelial cells of transplanted kidney, directly destroy target cells by activating complement, or lead to platelet aggregation, neutrophil infiltration and coagulation system activation through various complement cleavage fragments produced in the process of complement activation, and finally lead to severe ischemia and graft necrosis. Once hyperacute rejection occurs, there is no effective treatment, which will eventually lead to transplant failure. Therefore, inappropriate organ donors can be screened by ABO and HLa matching before transplantation to prevent hyperacute rejection.

(2) Acute rejection

Acute rejection is the most common rejection, which usually occurs within a few days to several months after transplantation and progresses rapidly. When acute rejection occurs in renal transplantation, it can be manifested as clinical symptoms such as elevated body temperature, local swelling and pain, decreased renal function, oliguria or even anuria, and increased white blood cells or lymphocytes in urine. Cellular immune response is the main cause of acute transplant rejection, and CD4+T(TH 1) cells and CD8+TC cells are the main effector cells. Even if HLA matching and immunosuppressive drugs are used before transplantation, 30% ~ 50% of transplant recipients will have acute rejection. Most acute rejection can be alleviated by increasing the dose of immunosuppressants.

(3) Chronic rejection

Chronic rejection usually occurs several months to several years after organ transplantation. The main pathological feature is the proliferation of endothelial cells in the capillary bed of transplanted organs, which narrows the arterial cavity and gradually fibrosis. Chronic immune inflammation is the main cause of the above histopathological changes. At present, there is no ideal treatment for chronic rejection.

Second, graft versus host reaction.

If the direction of immune attack is from the graft to the host, that is, the immune cells in the graft react to the tissue antigen of the host and cause tissue damage, it is called graft-versus-host reaction (GVHR). The occurrence of GVHR requires some specific conditions: ① the histocompatibility between the host and the graft is incompatible; ② The graft must contain enough immune cells; ③ The host is in a state of immunodeficiency or severe immunodeficiency. GVHR is mainly seen after bone marrow transplantation. In addition, GVHR can occur in different degrees when spleen and thymus are transplanted, and when newborns with immune deficiency receive blood transfusion.

Acute GVHR usually occurs within 10-70 days after bone marrow transplantation. GVHR can be avoided if T cells in bone marrow are removed, indicating that T cells in bone marrow are the main effector cells causing GVHR. However, clinical observation shows that after removing T cells from bone marrow, the success rate of bone marrow implantation also decreases, and the recurrence rate of leukemia and the infection rate of viruses and fungi also increase. This shows that T cells in bone marrow have graft anti-leukemia effect, which can overwhelm the remaining host immune cells and avoid the host's rejection of the graft. Under the condition that the host immune reconstruction is not completed, it can also play the role of anti-microbial infection. Therefore, selectively transplanting antigen T cells into the host and retaining the remaining T cells can not only avoid GVHR, but also retain its protective cellular immune function.

Development history of organ transplantation

Looking back on the history of medical development in the 20th century, organ transplantation is undoubtedly an enduring monument in the journey of conquering diseases. Among them, liver transplantation is the most difficult project, which requires not only a high-level surgical team, but also rich knowledge of related disciplines to provide patients with advanced liver disease with opportunities for regeneration.

1977 10 month, the first human orthotopic liver transplantation in China.

In July of 200 1 year, the first split liver transplantation was performed in China.

In 2004, from June, 5438 to June, 065438 10, Shanghai took the lead in carrying out combined transplantation of small intestine and liver.

From June, 2004 to February, 2004, the first combined transplantation of seven organs was performed in China.

In July, 2005, the first patient with acute fatty liver in pregnancy in China received a successful liver transplantation.

In September 2005, Shanghai took the lead in combining pancreaticoduodenectomy with liver transplantation.