Overview of Hematopoietic Stem Cells
Hematopoietic stem cell (HSC) also known as pluripotent stem cells, is a type of primitive hematopoietic cell in hematopoietic tissue. It can also be said that it is the original cell of all blood cells. That is, hematopoietic stem cells are differentiated and differentiated into different blood cell lines, and blood cells are further produced. Human hematopoietic stem cells first appeared in the 2-3 weeks of ovarian germination, and migrated to the liver and spleen in the early embryonic stage (2-3th month), and moved from the liver and spleen to the bone marrow in the fifth month. From the end of the embryo to the time of birth, the bone marrow becomes the main source of hematopoietic stem cells. Hematopoietic stem cells are the earliest, most, and most intensive research in stem cells. In recent years, important progress has been made in many research fields of hematopoietic stem cells. It has been successfully used in the clinical treatment of diseases such as leukemia and immunodeficiency.
Hematopoietic stem cells are the only source of blood cells in the body, present in bone marrow, cord blood, and peripheral blood, it has the ability to self-renew or self-sustain, high proliferative potential, and multi-directional differentiation potential. Let us introduce these three biological characteristics carefully. (1) Self-renew or self-sustain. Under normal conditions, HSC undergoes asymmetrical mitosis to form two daughter cells. One of them still maintains the characteristics of hematopoietic stem cells, namely self-renewal. Self-renewal makes the size of the stem cell pool (the number of stem cells) and quality constant, and is therefore called self-sustainment. Another sub-cell gradually changes its traits during mitosis, it becomes a progenitor cell, a precursor cell, and a mature blood cell of different lineages, replacing the cells that are consumed or senescent, thereby maintaining the number of various blood cells circulating. (2) High proliferative potential. In the bone marrow, HSC accounts for about 0.05% of bone marrow cells, and most of them are in the G0 phase. Under normal physiological conditions, less than 10% of HSCs are proliferating enough to maintain constant hematopoiesis. Radiotherapy and chemotherapy cause significant depletion of hematopoietic cell populations or HSCs can divide in large numbers under the influence of certain cytokines and HSC mobilizers, so that more HSCs enter the cell cycle. (3) multi-directional differentiation potential. HSC can not only differentiate into blood cell lines of various systems, such as erythroid cells, granulocyte cell lines, mononuclear-phagocytic cell lines, megakaryocyte cell lines, mononuclear-phagocytic cell lines, but also has plasticity and can be transformed into certain non-hematopoietic cells. Such as nerve cells, skeletal muscle cells, liver cells, vascular endothelial cells, and epithelial cells of various tissues.
Figure 1. Differentiation of hematopoietic stem cells
CD34 is a representative surface marker of hematopoietic stem/progenitor cells that is widely recognized, as the cells mature, they gradually decrease and disappear. In normal bone marrow, CD34+ cells account for about 1% to 3%. It can be further divided into two subgroups of CD34+ CD38- and CD34+ CD38+, among them, hematopoietic stem cells account for only a small part of the CD34+ CD38- cell population. Now we think that the sign of stem cells is CD34+, CD38-, HLA-, DR-, Lin-, Thy-1+, c-kit+, Scal-1+, LFA-1-, CD45, RA-, CD71-, Rho. Hematopoietic stem cell transplantation for the isolation of CD34+ cells by clinical application of immunosorbent assay and immunomagnetic beads separation has been successful. Another new hematopoietic stem/progenitor cell surface is now labeled as AC133, it can specifically bind to a monoclonal IgG antibody (molecular weight 120KD) against produced by a new hybridoma cell line. AC133 antigen is selectively expressed on the surface of CD34+ hematopoietic stem/progenitor cells in human fetal liver, bone marrow and peripheral blood, thus, AC133 can be used in place of CD34 as a marker for selection of hematopoietic stem/progenitor cells for sorting and transplantation.
Hematopoietic stem cells transplantation
In clinical treatment, using two important basic features of stem cell self-renewal and differentiation, already able to treat multiple diseases, and reconstitute hematopoietic function. Hematopoietic stem cell transplantation is performed by transplanting bone marrow cells to patient or hematopoietic stem cells isolated from peripheral blood and cord blood, which are externally cultured and expanded and transplanted to patients for reconstruction or restoration of the hematopoietic function and immune function of the recipient. Currently, hematopoietic stem cell transplantation includes autologous transplantation and allogeneic transplantation, autologous transplantation is divided into autologous bone marrow transplantation and autologous peripheral blood stem cell transplantation; allogeneic transplantation has allogeneic bone marrow cell transplantation and cord blood hematopoietic stem cell transplantation. Autologous bone marrow stem cell transplantation can reduce the incidence of rejection, but clinical transplantation is not easy to succeed, the main reason is that tumor cells are reinstated and tumor recurrence is caused.
Gene therapy for hematopoietic stem cells
Gene therapy refers to a technique and treatment for introducing a foreign gene or nucleic acid into the human body to prevent and treat diseases. In order for a cell carrying a gene of interest to be expressed chronically or permanently in a patient, it is necessary to select a cell that is self-renewing and self-sustaining in the body as a host cell. Hematopoietic stem cells are self-renewing and multi-directional, it is never depleted during normal hematopoietic in the body, and it can maintain the relative stability of genomic DNA during differentiation, thus becoming an ideal target cell for gene therapy of certain diseases. The advantages of using hematopoietic stem cells as target cells for gene therapy are as follows. (1) It is easy to obtain and is derived from the patient’s own or cord blood. (2) Strong self-renewal ability is conducive to long-term, stable expression of genes. (3) Hematopoietic stem cells have the ability to differentiate into various lines, because the differentiation cells can be distributed to various parts of the body along with the blood circulation, it is beneficial to the foreign genes carried by them to exert a greater therapeutic effect. (4) Hematopoietic stem cells, whether in the bone marrow or in circulating blood, can reach the target organ through the blood circulation. In recent years, with the maturity of hematopoietic stem cell collection, separation and purification, in vitro culture, amplification, and transplantation, the application of hematopoietic stem cells in gene therapy has been technically guaranteed. But because hematopoietic stem cells only account for 0.001% of bone marrow cells, so cultivation and separation and purification are not easy. For now, the biggest difficulty is that the gene introduction rate of human hematopoietic stem cells is very low. It is mainly due to the lack of receptors for recombinant retroviral vectors carrying therapeutic genes on the surface of human hematopoietic stem cells, moreover, most of the human hematopoietic stem cells are in the G0 quiescent phase, and the therapeutic gene loaded with the recombinant retroviral vector is difficult to integrate into the chromosomal genome of the quiescent cell. Many advanced laboratories at home and abroad are now conducting in-depth research on this. Once these problems are solved, the indications for hematopoietic stem cell transplantation can be greatly expanded; there will also be a new era in the treatment of tumors. However, we firmly believe that the future application of hematopoietic stem cells will make great progress.