Basic introduction
Hematopoietic stem cells represent the stem of hematopoietic stem cells (HSC), which is translated from the English word "stem", meaning "tree", "stem" and "source". Similar to the trunk, it can grow branches and leaves, blossom and bear fruit. Generally speaking, hematopoietic stem cells refer to immature cells and are the origin of all hematopoietic cells and immune cells. Therefore, it is a multifunctional stem cell, which is called "universal cell" in medicine and is also the ancestor cell of human body. Stem cells are primitive cells with self-replication and multi-directional differentiation potential, the origin cells of the body, and the progenitor cells that form various tissues and organs of the human body.
Hematopoietic stem cells have two important characteristics: first, they have a high degree of self-renewal or self-replication ability; Second, it can differentiate into all types of blood cells. Asymmetric division of hematopoietic stem cells: from one cell to two cells. One of the cells still maintains all the biological characteristics of stem cells, thus keeping the number of stem cells in the body relatively stable, which is stem cell self-renewal. The other one further proliferates and differentiates into various blood cells, precursor cells and mature blood cells, which are released into peripheral blood and perform their respective tasks until they die of aging. This process is ongoing.
Basic introduction of placental hematopoietic stem cells;
Placenta is a place for blood exchange between fetus and mother, which contains very rich blood microcirculation. Placenta is one of the earliest organs formed in the mother's uterus during human development. Placenta contains a large number of early stem cells, including abundant hematopoietic stem cells. These stem cells perform hematopoietic functions in the placenta. Hematopoietic stem cells contained in the placenta stripped after birth can differentiate into the ancestors of various blood cells (red blood cells, white blood cells, platelets, etc.). ), and injected into the body can play a hematopoietic function.
Edit the hematopoiesis principle of this paragraph
Hematopoietic stem cells are also called pluripotent stem cells. It is a group of primitive hematopoietic cells existing in hematopoietic tissue. It can also be said that it is the primitive cell of all blood cells (mostly immune cells). Hematopoietic stem cells are directionally differentiated and proliferated into different blood cell lines and further produce blood cells. Human hematopoietic stem cells first appeared in the yolk sac of the second to third week of embryonic age, and moved to the liver and spleen in the early embryo (second to third month), and moved from the liver and spleen to the bone marrow in the fifth month. From the end of embryo to birth, bone marrow becomes the main source of hematopoietic stem cells. It has multipotentiality, that is, it has two functions: self-replication and differentiation. In embryos and rapidly regenerated bone marrow, hematopoietic stem cells are mostly in the proliferation cycle; In normal bone marrow, most of them are at rest stage (G0 stage). When the body needs it, one part differentiates and matures, and the other part differentiates and proliferates, so as to keep the number of hematopoietic stem cells relatively stable. Hematopoietic stem cells further differentiate into directional stem cells of different blood cell lines. Directed stem cells are mostly in the proliferation cycle, and further differentiate into blood cell lines of various systems, such as red blood cell line, granulocyte line, mononuclear-phagocytic cell line, megakaryocyte line, lymphocyte line and so on. Lymphocytes differentiated from hematopoietic stem cells have two developmental pathways. One is that they differentiate and mature into thymus-dependent lymphocytes, that is, T cells, under the action of thymus and the catalysis of thymosin. The other is not affected by thymus, but by bursa of fabricius (birds) or cystic organs (mammals), and differentiates into cyst-dependent lymphocytes or bone marrow-dependent lymphocytes, that is, B cells. T cells and B cells induce cellular immunity and humoral immunity respectively. If hematopoietic stem cells are lacking in the body, it will cause serious immune deficiency.
Differentiation of hematopoietic stem cells Hematopoietic stem cells are the ancestors of blood cells (red blood cells, white blood cells, platelets, etc.). ), an incompletely differentiated cell, has good differentiation and proliferation ability. Stem cell transplantation can help many people with blood diseases, such as leukemia. [1] Leukemia is caused by malignant proliferation and non-apoptosis of primitive cells in hematopoietic system. The way to save leukemia is to kill all these malignant cells, but chemotherapy is inseparable. Killing normal hematopoietic stem cells while killing cancer cells leads to lack of blood cells in human body and endangers the life of patients. When patients need to eradicate leukemia, they must kill cancer cells at one time, but such a large dose of chemotherapy often kills few normal stem cells. In order to restore patients' hematopoietic function as soon as possible and save their lives, hematopoietic stem cells need to be infused, which is what we call bone marrow transplantation. However, although the success rate of autologous bone marrow transplantation is high and the rejection is small, leukemia cells will inevitably be mixed during collection, which will cause the source of recurrence in the future, so allogeneic bone marrow transplantation is sometimes needed. But not everyone's bone marrow can be transplanted If the difference of immune markers between two people is too big, it will cause too strong rejection, leading to the failure of transplantation and the death of patients. The stem cell samples collected in the blood center will be sent to the bone marrow bank for gene archiving. When a patient needs allogeneic bone marrow transplantation and his bone marrow match is similar to yours, the blood center will inform you to donate stem cells, that is, donate bone marrow. It's not as terrible as imagined, and it's harmless to the body. It just circulates your blood to a collection machine, which will automatically collect blood, just like donating blood.
Hematopoietic principle:
Hematopoietic stem cells are directionally differentiated and proliferated into different blood cell lines and further produce blood cells. Human hematopoietic stem cells first appeared in the yolk sac of the second to third week of embryonic age, and the placenta began to exert hematopoietic function in the fourth week. Hematopoietic function extends to the liver and spleen in the early embryo (2 ~ 3 months) and transfers from the liver and spleen to bone marrow in the fifth month. Placenta is an important hematopoietic tissue during embryonic development, and bone marrow becomes the main source of hematopoietic stem cells from the end of embryo to after birth. Hematopoietic stem cells have two functions: self-replication and differentiation. In embryos and rapidly regenerating hematopoietic tissues, hematopoietic stem cells are mostly in the proliferation cycle; In normal bone marrow, most of them are at rest stage (G0 stage). When the body needs it, one part differentiates and matures, and the other part differentiates and proliferates, so as to keep the number of hematopoietic stem cells relatively stable. Hematopoietic stem cells further differentiate into directional stem cells of different blood cell lines. Directed stem cells are mostly in the proliferation cycle, and further differentiate into blood cell lines of various systems, such as red blood cell line, granulocyte line, mononuclear-phagocytic cell line, megakaryocyte line, lymphocyte line and so on. Lymphocytes differentiated from hematopoietic stem cells have two developmental pathways. One is that they differentiate and mature into thymus-dependent lymphocytes, that is, T cells, under the action of thymus and the catalysis of thymosin. The other is not affected by thymus, but by bursa of fabricius (birds) or cystic organs (mammals), and differentiates into cyst-dependent lymphocytes or bone marrow-dependent lymphocytes, that is, B cells. T cells and B cells induce cellular immunity and humoral immunity respectively. If hematopoietic stem cells are lacking in the body, it will cause serious immune deficiency.
Hematopoietic stem cells are the ancestors of blood cells (red blood cells, white blood cells, platelets, etc.). ), an incompletely differentiated cell, has good differentiation and proliferation ability. Stem cells can help many people with blood diseases, such as leukemia. If the primitive cells of hematopoietic system have malignant proliferation, leukemia will be formed, and the treatment of leukemia is to kill all these malignant cells. However, chemotherapy not only kills cancer cells, but also kills normal hematopoietic stem cells, resulting in insufficient blood cells and endangering patients' lives. In order to restore the hematopoietic function of patients as soon as possible and save their lives, hematopoietic stem cells need to be injected. However, if the difference of immune markers between two people is too great, it will cause strong rejection, leading to the failure of transplantation and the death of patients. Autologous storage of hematopoietic stem cells can avoid this situation. Umbilical cord blood or placental hematopoietic stem cells can be stored at birth. When my patients need transplantation, they can directly apply for placental hematopoietic stem cells for the treatment of their own diseases.
Editing this paragraph mainly focuses on bone marrow transplantation technology.
The comparative diagram of hematopoietic stem cells in life science is one of the fastest developing disciplines in the 20th century, and it is also the most striking field in natural science.
1957 donar Thomas of the University of Washington, USA, found that transplantation of normal bone marrow into patients can treat hematopoietic dysfunction. The discovery of this technology won Donna Thomas the Nobel Prize.
This technology was quickly recognized by the whole world and became the main means to treat leukemia and other diseases. The discovery and application of hematopoietic stem cell transplantation technology has brought new hope for human beings to overcome diseases. In particular, the Ark of Life project, which began in 265438+early 20th century, made a breakthrough in the discovery and application of hematopoietic stem cell transplantation technology.
treat a disease
Hematopoietic stem cell transplantation is a major breakthrough in modern life science. Hematopoietic stem cell transplantation can treat 75 fatal diseases, such as hematological malignancies, some malignant tumors and some hereditary diseases. Include acute leukemia, chronic leukemia, myelodysplastic syndrome, hematopoietic stem cell diseases, myeloproliferative diseases, lymphoproliferative diseases, macrophage diseases, hereditary metabolic diseases, histiocytic diseases, hereditary red cell diseases, hereditary immune system diseases, hereditary platelet diseases, plasma cell diseases, thalassemia, non-blood system malignant tumors, acute radiation sickness and the like.
Because of hematopoietic stem cell transplantation technology, thousands of patients with these diseases all over the world have rekindled their hopes for life.
Use of placental hematopoietic stem cells:
The content of hematopoietic stem cells in placenta tissue is 8- 10 times that of umbilical cord blood, which can be used by children for many times and even provided to many adult patients for treatment. Placental hematopoietic stem cell transplantation can effectively solve the technical problems such as the shortage of adult bone marrow or mobilized peripheral blood and the shortage of umbilical cord blood hematopoietic stem cells, and is expected to replace bone marrow, mobilized peripheral blood and umbilical cord blood for allogeneic or allogeneic hematopoietic stem cell transplantation.
Placental hematopoietic stem cell transplantation can be used to treat a variety of hematological diseases and immune system diseases, including hematological malignancies (such as leukemia, multiple myeloma, myelodysplastic syndrome, lymphoma, etc.). ), hemoglobinopathy, bone marrow hematopoietic failure (such as aplastic anemia), congenital metabolic diseases, congenital immunodeficiency diseases, autoimmune diseases and other diseases.
Edit this donation to introduce the collection method.
1. After the newborn is delivered, clamp the umbilical cord with two hemostatic forceps at a distance of 10 cm, then cut the umbilical cord between the two clamps and ligate it. It is best to disinfect the umbilical cord stump, umbilical cord root and its surroundings with 75% ethanol, and the newborn will be taken away for normal treatment.
2. After the placenta is delivered, the umbilical cord at the baby end of the placenta is ligated with medical surgical suture or other suitable materials.
3. Wash the placenta umbilical cord 1-2 times with 0.9% physiological saline to remove amniotic fluid and meconium from the placenta and avoid the placenta umbilical cord from contacting with other objects.
4. Put the collected placental umbilical cord into a sterile disposable placental collection box, and cover the box cover to ensure that the collected liquid does not pass through the placenta.
stored procedure
After the placenta is collected, it will be transported to the stem cell bank within a limited time, and professional technicians will carry out technical processes such as separation, extraction and detection of placental hematopoietic stem cells until the final test results confirm whether the obtained stem cells have long-term preservation value.
Preservation and duration
At present, the commonly used stem cell preservation technology in the world is to preserve the obtained stem cells at a cryogenic temperature of-196℃. China is in the forefront of the world in the field of hematopoietic stem cell cryopreservation and anti-injury. Medical research and clinical practice have proved that cells preserved for more than 100 years are still active, while stem cells have been preserved for decades. Placental stem cell bank is responsible for the activity of placental hematopoietic stem cells stored in the stem cell bank during the contract period signed with customers.
safe
Placenta collection is simple and easy, and will not cause any uncomfortable feeling, nor will it have any adverse effects on mother and newborn. In the past, placenta was usually discarded as waste. Extracting hematopoietic stem cells from placenta for preservation is a valuable life resource regeneration.
The data show that the hematopoietic stem cell gene is stable, not easy to mutate, animal experiments prove that it has no tumorigenicity and tumor promotion, and it is safe and reliable to use, and it has a good therapeutic effect on diseases within the scope of indications, which is superior to traditional medical means.
Physiology will not harm health.
There are many kinds of blood cells in human blood, such as red blood cells, white blood cells and platelets. They all have a life span ranging from 120 days to 36 hours, and they are constantly metabolized. They all come from an ancestral cell, which we call hematopoietic stem cells. Hematopoietic stem cells have high self-renewal and self-replication ability, and can differentiate into various blood cells. Hematopoietic stem cells have strong regenerative ability. Blood loss or donation of hematopoietic stem cells can stimulate bone marrow to accelerate hematopoiesis. 1-2 weeks, various components in the blood can be restored to the original level.
After school-age and healthy volunteers donate hematopoietic stem cells, the decrease in the number of blood cells will prompt the bone marrow to release the reserved white blood cells, stimulate the hematopoietic function of bone marrow, and promote the formation of blood cells without affecting health.
Hematopoietic stem cells in human body mainly exist in the grid between the bone marrow cavity of long bone and cancellous bone of flat bone, which is a red spongy tissue called red bone marrow.
As soon as a person is born, red bone marrow fills the bone marrow cavity of the whole body. With the increase of age, fat cells increase, and a considerable part of red bone marrow becomes yellow bone marrow. This change is because adults do not need all bone marrow to participate in hematopoiesis, and some bone marrow hematopoiesis is enough to supplement the needed blood. When the body is severely ischemic, part of the yellow bone marrow can be turned into red bone marrow to continue hematopoiesis.
Practical safety
More than 700 cases of hematopoietic stem cells/KLOC-0 have been collected in Chinese mainland, with no correlation and many correlations.
Taiwan Province Province has collected more than 800 cases of hematopoietic stem cells (mostly bone marrow).
Internationally, the United States has collected more than 20,000 cases of hematopoietic stem cells (mostly bone marrow);
Japan has collected more than 5,500 cases of hematopoietic stem cells (all bone marrow).
According to years of clinical observation and international reports, there is no case of donor injury caused by collecting peripheral blood hematopoietic stem cells. After the collection is completed, some slight pain and discomfort will soon disappear.
Mobilizing agent security
It is easy to collect hematopoietic stem cells from peripheral blood, so this method is often used to donate hematopoietic stem cells in China. However, under normal physiological conditions, the number of peripheral blood hematopoietic stem cells is small, which can not meet the needs of transplantation. For example, injection of cell mobilization agent can increase the number of hematopoietic stem cells in peripheral blood by 20~30 times. The currently used cell mobilization agent is "granulocyte-macrophage colony stimulating factor (GM-CSF)"
) ",in addition to increasing the number of hematopoietic stem cells in peripheral blood, it also has the function of assisting heart function. According to years of clinical observation and international reports, no harm and side effects to human health have been found so far.
Collection standard
The bone marrow of adults (18 ~ 45 years old) is generally about 3000 grams, most of which are in the bone marrow cavity. An adult patient collects 50-200 ml of hematopoietic cell suspension for no more than 2 times. In general, the circulating blood volume is not less than
10000ml. CD34+ >; 2 × 106/kg, MNC & gt5× 108/ kg. CD34+ was detected every day.
The amount collected during peak hours has no adverse effect on the blood donors themselves.
Mature technology
China Bone Marrow Bank has transplant hospitals and collection hospitals (centers) approved by the expert committee. Collecting hematopoietic stem cells in such hospitals is as simple and safe as collecting blood components.
The instruments used in the whole process are strictly disinfected and used once, which ensures the safety of donors.
Edit this bone marrow function
Blood is a red, opaque and viscous liquid composed of plasma (the liquid part of blood) and blood cells (erythrocytes, granulocytes, lymphocytes, monocytes, platelets, etc.). The total blood volume of normal adults is about 8% of their body weight. Blood is a continuous stream in blood vessels, which is a "river" for transporting nutrients, carrying metabolites, regulating internal environment balance and exercising defense functions in the human body. People's understanding of blood is also gradually deepening. The ancient Egyptians advocated bathing blood to restore health. Before 1900 discovered ABO blood group of red blood cells, many people suffered from severe hemolysis and even died because of blood group incompatible transfusion. 1929 bone marrow puncture needle was invented, and bone marrow cells became an important part of hematology research.
The number and function of blood cells in normal people are relatively constant. This constant is the dynamic balance of metabolism, that is, aging and dead cells are often replaced by new cells. For example, the average life span of human red blood cells is about 120 days, and the life span of platelets is about 7- 10 days. A normal adult has about 10 red blood cells aging and dying every day; There are also a similar number of red blood cells.
Adult hematopoietic organs are mainly limited to bone marrow, spleen and lymph nodes. However, the main function of spleen and systemic lymph nodes after birth is to promote the secondary proliferation of lymphocytes, that is, the immune response of lymphocytes to reproduce after contact with antigens. Therefore, the hematopoietic function of bone marrow is particularly important. After birth, bone marrow is the only place to produce red blood cells, granulocytes and platelets under normal circumstances, and bone marrow also produces lymphocytes and monocytes.
Bone marrow is a spongy tissue, which exists between the bone marrow cavity of long bones (such as humerus and femur) and the cancellous bone of flat bones (such as ilium). The bone marrow that can produce blood cells is reddish and is called red bone marrow. As soon as a person is born, red bone marrow fills the bone marrow cavity of the whole body. With the increase of age, fat cells increase, and a considerable part of red bone marrow is replaced by yellow bone marrow. Finally, there is almost only red bone marrow in the bone marrow cavity of flat bone. This change may be due to the fact that adults do not need all bone marrow cavity hematopoiesis, and some bone marrow cavity hematopoiesis is enough to supplement the needed blood cells. When the body is seriously ischemic, part of yellow bone marrow can be replaced by red bone marrow, and the hematopoietic capacity of bone marrow is significantly improved.
In the past 30 years, the research on hematopoiesis has developed rapidly. It has been proved that there are hematopoietic pluripotent stem cells in human bone marrow, the number of which is less than 1% of the total number of bone marrow cells, and they have high self-renewal ability. It can differentiate into progenitor cells of various blood cell systems (such as lymphoid stem cells and granulocyte stem cells), and then differentiate and proliferate into various primitive and mature blood cells. Finally, these mature blood cells enter the blood through the bone marrow and play their respective physiological roles. Human hematopoietic stem cells have different functions because of their different locations. Part of it exists in the stem cell pool, which is the storage of human hematopoietic cell regeneration to meet the needs of hematopoiesis under various conditions; The other part exists in the proliferation pool, and these cells are constantly proliferating and updating to make up for the lack of blood cells caused by cell aging or loss and maintain the blood flow balance of the human body.
The hematopoietic capacity of bone marrow is extremely strong, and the highest hematopoietic capacity of bone marrow can reach 9 times of normal hematopoiesis. If only one tenth of the bone marrow is preserved, normal hematopoietic function can be completed, so a small number of bone marrow donors have no effect on the human body. The hematopoietic tissue of human body has a strong compensatory function. After extracting part of bone marrow, hematopoietic stem cells will accelerate their proliferation and completely return to their original level within a week or two. Therefore, donors will not only affect their hematopoietic function, but also exercise their hematopoietic system and be more energetic.
Edit the cell source of this paragraph.
Usually, hematopoietic stem cells come from three sources:
1, bone marrow hematopoietic stem cells.
2. Peripheral hematopoietic stem cells.
3. Umbilical cord blood hematopoietic stem cells.
4. Placental-derived hematopoietic stem cells
At present, Chinese bone marrow bank mainly collects hematopoietic stem cells from peripheral blood.
At present, only Han's joint collection of placental hematopoietic stem cells in China has obtained relevant national patent certificates.
Comparison of hematopoietic stem cells from different sources;
The sources of hematopoietic stem cells are bone marrow hematopoietic stem cells, peripheral blood hematopoietic stem cells, umbilical cord blood hematopoietic stem cells and placental tissue hematopoietic stem cells. The comparison of cells from four sources is as follows.
Transplantation method peripheral blood hematopoietic stem cells bone marrow hematopoietic stem cells cord blood hematopoietic stem cells placental hematopoietic stem cells
Hematopoietic stem cells with relatively simple components have other blood components besides hematopoietic stem cells, besides hematopoietic stem cells, there are other blood components and other types of stem cells.
Methods: Blood vessels of upper arm were collected without hospitalization and anesthesia, and mobilization agent was injected painlessly before collection. Drilling medullary bone requires hospitalization and anesthesia, and it is not painful to inject mobilization agent. Collect umbilical cord blood and placenta.
Transplant application is generally less, only suitable for children under 30KG, and can meet the needs of 1-2 adults.
The matching degree is strict, not strict, not strict.
The reaction after transplantation is serious, more serious and lighter.
Do you need medication? No, no, no.
Low cost, high cost, high cost.
The collection and recovery time is 2-4 days and half a year-
Save without saving without saving entity save entity save.
The content of hematopoietic stem cells in placenta tissue is 8- 10 times that of cord blood, which can be used by children for many times, and may even be treated by 1-2 adult patients. At the same time, it effectively solves the technical problems such as insufficient source of bone marrow or mobilized peripheral blood and insufficient quantity of cord blood during transplantation, and is expected to replace bone marrow, mobilized peripheral blood and cord blood for allogeneic or homologous (children's own) hematopoietic stem cell transplantation.
Edit the use of hematopoietic stem cells in this paragraph.
Hematopoietic stem cells are one of the blood components, and are the initial cells that produce various blood cells, also known as hematopoietic pluripotent stem cells, which exist in bone marrow, embryonic liver, peripheral blood and umbilical cord blood. It not only has high self-renewal ability, but also has the ability to further differentiate the progenitor cells of each system. Modern blood transfusion is to use these two abilities to suppress the recipient's immune system with radiation or large doses of chemical drugs, and then the donor's hematopoietic stem cells "settle, differentiate and proliferate" in the recipient's bone marrow, which is hematopoietic stem cell transplantation. Hematopoietic stem cell transplantation includes bone marrow transplantation (BMT), fetal liver hematopoietic cell transplantation, peripheral blood stem cell transplantation (PBSC) and umbilical cord blood hematopoietic cell transplantation.
BMT is the most commonly used hematopoietic stem cell transplantation in clinic. Clinically, it can be divided into three types: homologous BMT(SBMT), allogeneic BMT and autologous BMT(ABMT). The first two are mainly used for neoplastic hematological diseases, hereditary hematological diseases and some metabolic diseases, while autologous BMT is mostly used for leukemia and solid tumor patients. Umbilical cord blood can be used for allogeneic transplantation and autologous hematopoietic reconstruction. All diseases that meet BMT indications can be replaced by umbilical cord blood transplantation. There are two clinical applications of human fetal liver hematopoietic cells, one is fetal hepatocyte infusion (FLCI) and the other is fetal liver transplantation (FLT). According to the comprehensive literature, the diseases of fetal hepatocyte infusion include aplastic anemia, leukemia, paroxysmal nocturnal hemoglobinuria, Fanconi anemia, acute agranulocytosis, severe hepatitis or decompensated cirrhosis, solid tumor in chemotherapy, renal anemia and so on. Diseases treated by fetal liver transplantation include severe combined immunodeficiency, leukemia, aplastic anemia, thalassemia, advanced lymphoma and acute radiation sickness. Fetal hepatocytes are used in clinic because of their convenient materials, safe infusion and no serious graft-versus-host disease, which shows a certain prospect. The clinical application reports of peripheral blood hepatocyte transplantation include the treatment of acute leukemia, chronic myeloid leukemia and malignant tumor. Compared with hematopoietic stem cell transplantation of bone marrow and embryonic liver, peripheral blood hepatocyte transplantation has the advantages of early hematopoietic and immune function reconstruction. Low radiation sensitivity and high implantation rate. The residual tumor cells in peripheral blood are less than those in bone marrow. Convenient collection, no need for bone marrow puncture, easy to accept.
Due to the progress of transplantation immunology, human hematopoietic stem cell transplantation has entered a new stage of development and become an important part of cell engineering.