The concept of hematopoietic stem cell (HSC) is a kind of adult stem cell, which is the starting cell of hematopoietic and immune system. 0.1% in peripheral blood. Theoretically, as long as there is one HSC, it is possible to form a complete hematopoietic and immune system. In order to safely reconstruct a functional blood and immune system throughout the body in a short period of time, clinically a significant number of HSCs are required for successful transplantation. Hematopoietic stem cell transplantation (HSCT) involves removing a certain number of hematopoietic stem cells from the donor as a graft and using a pretreatment regimen consisting of a certain dose of chemotherapy and/or radiotherapy to remove the diseased hematopoietic and immune systems of the recipient, i.e., to remove tumor cells, abnormal clonal cells, and abnormal pathogenesis from the recipient. Then the donor’s hematopoietic stem cells are transfused and transplanted into the recipient to rebuild the recipient’s hematopoietic and immune systems for the purpose of treating the disease. To date, hematopoietic stem cell transplantation has successfully saved the lives of tens of thousands of patients. Hematopoietic stem cell transplantation is a systemic project that gradually developed and grew in the 1950s into a unique fringe discipline at the intersection of hematology, oncology, transplantation immunology, cell biology, radiobiology, organ transplantation, and other multidisciplinary disciplines. Since 1958, when Mathe first performed bone marrow transplantation on nuclear accident victims, hematopoietic stem cell transplantation has developed rapidly with advances in human histocompatibility antigen (HLA) matching and transplantation techniques, as well as improvements in supportive care. The old term “bone marrow transplantation” has long been replaced by the new concept of “hematopoietic stem cell transplantation”. According to the donor, hematopoietic stem cell transplantation can be divided into autologous transplantation (Auto-), syngeneic transplantation between identical twins (Syn-), and allogeneic transplantation (Allo-); syngeneic allogeneic transplantation can be divided into sibling donor transplantation and non-sibling donor transplantation. donor transplantation and unrelated donor transplantation. Hematopoietic stem cell transplantation can be divided into bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), fetal liver cell transplantation (FLT), and cord blood transplantation (CBT) according to the organ of origin of the hematopoietic stem cells. Depending on the pre-treatment before transplantation, HSCT can also be divided into clear marrow and non-clear marrow transplantation. Depending on whether the graft is purified or not, HSCT can be divided into general HSCT, de-T transplantation, and purified CD34+ cell transplantation. According to the degree of HLA compatibility between donors and recipients, they can be divided into HLA compatible transplantation, HLA semi-compatible transplantation and HLA incompatible transplantation. The first human hematopoietic stem cell transplantation was performed in 1939, when a patient with aplastic anemia received bone marrow from his brother with the same blood type and died 5 days later. In 1965, a patient received bone marrow from six blood donors after chemotherapy and radiation therapy and obtained durable implantation. Since then, allogeneic bone marrow transplantation (Allo-BMT) has developed rapidly, and autologous bone marrow transplantation (ABMT) began in the 1970s. With the maturation of hematopoietic stem cell mobilization with cytokines and hematopoietic stem cell monoculture with blood cell separators, autologous peripheral hematopoietic stem cell transplantation (APBSCT) and allogeneic peripheral hematopoietic stem cell transplantation (Allo-PBSCT) emerged in 1985. For donors, PBSCT does not require anesthesia and multi-site puncture to collect stem cells, which is safer and more acceptable than BMT; the graft is less contaminated by tumor cells, and the hematopoietic reconstruction is faster after transplantation, and the chance of infection and bleeding is reduced. It is also a new source of stem cells for patients whose bone marrow has been infiltrated by tumors or irradiated. According to the International Bone Marrow Transplant Registry (IBMTR), the European Group for Blood and Marrow Transplantation (EBMT) and the Australian Collaborative Committee for Organ Transplantation and Donation (ACCORD), the number of APBSCT and Allo-PBSCT has increased rapidly since 1995 and is now gradually replacing bone marrow transplantation. In October 1988, the Hospital of Saint-Louis in Paris, France, in cooperation with the Indian University School of Medicine in the United States, was the first in the world to apply HLA-matched sibling cord blood transplantation to treat a patient with Fanconi anemia successfully. Since then the basic research and clinical application of CBT has received more and more attention, an International Cord Blood Transplant Registry (ICBTR) has been established, and cord blood banks have been set up in many countries. In 1990, Dr. E.D. Thomas was awarded the Nobel Prize in Medicine for his outstanding contribution to bone marrow transplantation. The first allogeneic bone marrow transplantation was successfully performed in China in 1981, and since then, bone marrow transplantation in China has developed significantly, and the number of transplantation cases has increased year by year. In 1999, the first adult cord blood transplantation for leukemia was successful, and in recent years, cord blood banks have been established in some regions. The indications and efficacy of hematopoietic stem cell transplantation At present, hematopoietic stem cell transplantation has become the main method and fundamental way to cure many malignant hematological diseases, certain malignant solid tumors, immune and genetic diseases. The indications for allogeneic HSCT are: acute and chronic lymphocytic leukemia acute and chronic myeloid leukemia non-Hodgkin’s lymphoma Hodgkin’s lymphoma myelodysplastic syndrome multiple myeloma and other plasma cell tumors severe aplastic anemia sex-linked severe disease combined with immunodeficiency and anaplasmosis sex-linked lymphoproliferative disorders Wisket-Aldrich syndrome Chediak-Higashi syndrome chronic granulomatous disease erythrocytic phagocytic lymphohistiocytosis osteosclerosis cartilaginous hairy dysplasia thalassemia sickle cell anemia adenosine deaminase defect and purine nucleotide phosphorylase defect type I Gaucher disease Fanconi anemia congenital dyskeratosis adrenal cerebral leukodystrophy and heterozygous cerebral leukodystrophy mucopolysaccharidoses (sex-linked, Sly syndrome), Ltsch-Nyhan syndrome (sex-linked) malignant histiocytosis incidental acute radiculopathy indications for autologous hematopoietic stem cell transplantation are: acute lymphocytic leukemia, relapsers chronic lymphocytic leukemia acute myeloid leukemia, relapsers chronic myeloid leukemia, acute stage non-Hodgkin’s lymphoma, low grade malignant Hodgkin’s lymphoma, CR1; refractory myelodysplastic syndromes multiple myeloma and other plasma cell tumors non-chronic myeloid leukemia myeloproliferative disorders such as proerythroblastosis, thrombocythemia and primary myelofibrosis solid tumors: breast cancer, germ cell tumors, ovarian cancer, glioma, small cell lung cancer, non-small cell lung cancer autoimmune diseases: thrombocytopenic purpura, systemic sclerosis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, amyloidosis. V. Complications of hematopoietic stem cell transplantation 1. After patients receive hematopoietic stem cell transplantation, the chance of infection increases significantly due to the suppression of immune function, with an incidence of 50%-80%. Infectious lesions may occur in any part of the body and may arise from complications of transplantation operations, activation of potentially infectious agents, and exposure to new pathogens in the environment. The pathogens that cause infections include bacteria, fungi, viruses, and parasites. Infection remains one of the major factors currently affecting the long-term survival of transplanted individuals. 2. Graft failure Graft failure is one of the most serious early complications of hematopoietic stem cell transplantation, especially Allo-HSCT. Due to the failure of graft implantation and hematopoietic reconstruction, the clinical presentation of patients with severely depressed complete blood picture with bone marrow emptiness or hypoproliferative, heavy complications of infection and bleeding, difficult management and high mortality. However, with the continuous progress of transplantation technology, the incidence of graft failure has been reduced to less than 5%, or even lower. GVHD is a major complication of Allo-HSCT and a cause of death, and is associated with immunogenetic differences between the donor and recipient. Chronic GVHD is a systemic disease similar to autoimmune disease, often involving multiple organs. 4. Hepatic veno-occlusive disease (VOD) VOD is one of the most serious complications of hematopoietic stem cell transplant pretreatment toxicity. Most of them appear within 3 weeks after transplant pretreatment, with clinical manifestations of hepatomegaly, jaundice, and water retention as the main manifestations. The mortality rate of moderate and severe VOD is high, and there is a lack of specific treatment methods. 5, hemorrhagic cystitis Hemorrhagic cystitis is also one of the common complications after HSCT, with clinical manifestations of varying degrees of hematuria. 6.Distant comorbidity of HSCT mainly involves: respiratory and pulmonary diseases, hypothyroidism, hypogonadism, cataract, secondary tumor and so on. Conventional clear marrow transplantation uses high-dose radiotherapy/chemotherapy as pretreatment protocol, which makes the transplantation process very risky, such as: prolonged severe hematopoietic suppression can cause cerebral hemorrhage, pulmonary hemorrhage, and bacterial/fungal sepsis, which often leads to early death; high-dose radiotherapy not only easily causes radiation pneumonia, hepatic vein occlusion syndrome, cataract and other serious complications. High-dose radiotherapy is not only prone to serious complications such as radiation pneumonia, hepatic vein occlusion syndrome, cataracts, but also affects the reproductive function of patients, causing infertility in young patients after transplantation. In addition, the incidence and severity of GVHD are high; patients are slow to rebuild their immune function after transplantation and are prone to recurrent infections; all of these seriously affect the quality of patients’ survival after transplantation. Moreover, patients who are older than 50 years old, frail, and combined with other organ dysfunctions are excluded from conventional transplantation treatment, but clinically a significant proportion of patients are mostly in their 50s, 60s, or even older at the time of onset. In 1998, scholars from the United States and Israel proposed the concept and method of “non-cleared marrow HSCT”. Non-clear marrow HSCT is not only well tolerated by patients, but also has minimal pretreatment-related complications; if a non-clear marrow pretreatment regimen without radiotherapy is used, complications such as radiation pneumonia, cataract, reproductive dysfunction, etc. can be completely avoided. Complications such as radiation pneumonia, cataracts, and reproductive dysfunction can be completely avoided with a non-cleared marrow pretreatment regimen without radiotherapy. Compared with clear marrow transplantation, hematopoietic reconstruction after non-clear marrow transplantation is rapid, more than 10 days or even 20 days earlier than clear marrow transplantation, which greatly shortens the period of myelosuppression and significantly reduces early mortality, making HSCT safer and less risky; in addition, due to the reduced impact on the function of vital organs in the body, many older, frail patients with combined damage to other organs can In addition, because of the reduced impact on the function of vital organs, many older, frail patients with combined impairment of other organs can benefit from HSCT treatment, and in young, infertile patients, their reproductive function is not affected after transplantation. More importantly, the incidence and severity of GVHD after transplantation are significantly reduced due to the enhanced immunomodulatory treatment before and after transplantation, and more patients do not need to take long-term immunosuppressive drugs after transplantation. At present, non-cleared marrow transplantation has become one of the important directions of HSCT research; especially in the field of haploidentical HSCT research, the non-cleared marrow transplantation model has become the most promising method to solve the “bottleneck” problem that restricts the breakthrough of haploidentical HSCT, i.e., to effectively reduce the incidence of severe GVHD. VII. Development and Prospects of HSCT As the research on HSCT progresses, more and more non-hematologic diseases, in addition to hematologic diseases, become indications for autologous and/or allogeneic HSCT. For example, Auto-HSCT after high-dose immunosuppressive therapy for severe autoimmune diseases has been developed as a promising treatment method and has become a hot research topic in rheumatology; Auto-HSCT has been used as the preferred option for the treatment of refractory autoimmune diseases as non-malignant diseases. Different from the supportive role played by Auto-HSCT in the treatment of certain malignant solid tumors, Allo-HSCT can induce graft-versus-tumor (GVT) effect after Allo-HSCT; in recent years, Allo-HSCT has been applied in the treatment of renal cell carcinoma and gastrointestinal tract tumors (such as gastric cancer, liver cancer, colorectal cancer, pancreatic cancer, esophageal cancer); studies have shown that Allo-HSCT induces the GVT effect by GVT effect, improved the therapeutic efficacy of mid- to late-stage tumors, improved patient survival quality and prolonged patient survival time. In addition, it is gradually recognized that Allo-HSCT can be used as a technical platform to support other organ transplantation. after Allo-HSCT, the formation of donor-recipient chimeras can be induced in the recipient, so that the recipient develops donor-specific, lifelong tolerance; at that time, other tissue or organ transplantation can be performed, which can reduce the intensity of immune rejection occurrence The intensity of immune rejection can be reduced and thus the survival rate of the transplanted organ can be improved. Gene therapy is the process of transferring an exogenous gene into a target cell to correct or treat a disease by expressing it in the patient. It has a promising future in the treatment of monogenic genetic diseases, malignant tumors, severe immunodeficiencies and infectious diseases. Hematopoietic stem cells are one of the ideal target cells for gene therapy because they are easy to obtain, easy to culture in vitro, easy to implant back into the patient and survive, and have a high self-renewal capacity. Exogenous genes are transferred into hematopoietic stem cells collected from patients, and then transfused back to patients to treat diseases by expressing them in vivo. Once this breakthrough in stem cell gene therapy technology is achieved, it will definitely have a profound impact on the somatic cell therapy for human diseases. So far, hematopoietic stem cells have been used for gene therapy for adenosine deaminase deficiency, Gaucher disease, HIV infection and cancer