Dysfunction or structural damage of human tissues and organs can cause disease. Dysfunction, that is, dysfunction or disorder of physiological function, cannot perform normal physiological function, but it does not involve substantial damage to tissues and organs. When the body's endocrine system and immune system malfunction, it will cause various diseases. When the function of the immune system is enhanced, allergic reactions may occur; while the function is reduced, which may cause pathogen invasion and tumor cells to escape from immune surveillance. The same is true of the endocrine system, for example, excessive thyroid secretion can lead to hyperthyroidism; and insufficient blood supply can cause hypothyroidism. Dysfunction of human tissues and organs, if not repaired for a long time, will induce the formation of major diseases. The damage of tissue and organ structure caused by internal pathological factors or external physical, chemical, biological and other factors, leads to dysfunction. Diseases caused by tissue organ dysfunction or structural damage can be treated by stem cell transplantation. The transplanted stem cells can repair dysfunctional tissues or regenerated damaged tissues and organs; meanwhile, the degree of repair or regeneration also determines the clinical treatment effect.
Stem cells are a kind of cells with the potential for self-renewal and multi-directional differentiation. They have good application prospects in many fields such as regenerative medicine. Currently, there are more than 5,000 registered stem cell clinical studies.
According to the developmental stage, stem cells can be divided into embryonic stem cells (ESCs) and adult stem cells (ASCs). ESCs come from the inner cell mass of the blastocyst stage. They have unlimited proliferation and three germ layer differentiation potentials. They have been the focus of tissue engineering and regenerative medicine. However, due to immune rejection and other issues. Induced pluripotent stem cells (i PSC) are derived from adult cells through reprogramming and have the same three germ layer differentiation potential as embryonic stem cells, which solves the risk of immune rejection of ESCs, but there is a low induction efficiency. For problems such as poor stability, scientists have been looking for a more optimal induction scheme. ASCs include: hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), neural stem cells, skin stem cells, and other precursor cells. ASCs have the ability to differentiate into specific tissues and cells. They exist in a variety of tissues and organs. They have great potential in tissue damage repair and disease treatment, and are the focus of regenerative medicine.
Regarding the mechanism of stem cell therapy, there are mainly the following views: (1) Replacement repair, because stem cells have the potential of self-replication and differentiation, totipotent stem cells and pluripotent stem cells can differentiate into nerve cells, skeletal muscle cells, peripheral blood mononuclear cells , Chondrocytes, skin epithelial cells, cardiomyocytes, vascular endothelial progenitor cells, etc. Therefore, the mechanism of stem cell therapy is related to cell differentiation and replacement. (2) Paracrine function, stem cells can secrete some trophic factors (such as VEGF, HGF, TNF-α, BMP-2, b-FGF, TGF-β, etc.) to regulate the internal environment. Mesenchymal stem cells often play this way effect. In addition, there are some indirect use of stem cells to regulate immune function. For example, after organ transplantation, mesenchymal stem cell treatment is performed to prevent rejection, that is, the occurrence of graft-versus-host disease (GVHD), and improve the success rate of organ transplantation. At present, the mechanism of stem cell therapy is still under continuous research and improvement, and multiple mechanisms also exist.
1. The clinical application of stem cells
1.1. Nervous system disease
In central nervous system diseases, there are a certain number of neural stem cells. In 1965, new neurons were found in the hippocampus of adult mice. At present, there is evidence that neural stem cells/precursor cells are present in brain tissue, mainly concentrated in the lateral ventricle, subependymal zone, and hippocampal dentate gyrus. These endogenous neural stem cells are few in number and have little effect on nerve repair after injury. Therefore, transplantation of exogenous stem cells has become the main strategy to repair the nervous system. Clinical studies have found that in the hippocampus area of mice, specific injection of stem cells at the injection site to repair local neural circuits can replace the reduced neurotransmitters, which gives new hope for the treatment of Parkinson's disease, Alzheimer's disease, Huntington's disease and other diseases. The current treatment of stem cells in the nervous system mainly includes: cerebral infarction, spinal cord injury, cerebral palsy in children, multiple sclerosis, and other neurodegenerative diseases (Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis), etc. The cells used include mesenchymal stem cells, neural stem cells, site-specific neural precursor cells and the like. In terms of the mechanism of MSCs treatment of stroke, it was early thought that stem cell differentiation and replacement played a role, but animal studies have found that only 2% of stem cells transplanted in the brain can survive. At the same time, intravenous injection can also play a role, and there is also a rat ventricle study on the internal injection of stem cell culture medium (without stem cells) to improve stroke symptoms. Therefore, it is proposed that the mechanism of its function is mainly related to the secretion of trophic factors (such as BDNF, VEGF, TGF). In the field of the nervous system, most clinical studies have confirmed that stem cells are safe for the treatment of neurological diseases, but their effectiveness varies from study to study. The reasons for the different efficacy are mainly related to the severity of the disease, the type of cells, the transplantation part and the transplantation route. Stereotactic equipment for stem cell transplantation can improve the success rate.
1.2. Heart disease
Exogenous stem cell transplantation has great potential for the treatment of heart diseases. The application of stem cells in heart diseases mainly focuses on myocardial infarction and ischemic cardiomyopathy. In the process of infarction, a large number of ischemic necrosis of myocardial cells, which in turn leads to a decline in cardiac contractility, severe heart failure may occur. Currently used stem cells include bone marrow MSCs, myocardial precursor cells, and i PSC. Among them, the application of bone marrow mesenchymal stem cells is the most mature, and clinical studies of small samples have confirmed the therapeutic effect of intracoronary injection of MSCs on myocardial infarction, which can improve left ventricular contractile function and reduce myocardial fibrosis. It is related to secretion of trophic factors, inhibition of myocardial apoptosis, regulation of immunity, and induction of angiogenesis. IPSC cells can differentiate into cardiomyocytes and replace damaged myocardium, and have been seen to be superior to MSCs in mammalian pigs, but no long-term survival of stem cells in the myocardium has been found. It is speculated that the main mechanism of their role is still aside secretory effect. In addition, IPSC faces a low rate of cardiomyocyte differentiation in vivo, there is a risk of tumorigenicity and arrhythmia, and clinical application requires caution.
To be continued in Part Two…