In recent years, the number of patients with advanced renal insufficiency is increasing rapidly, which has become a worldwide medical problem. Kidney transplantation and dialysis are traditional basic treatment methods. Dialysis has various complications, and it is only a substitute for filtration function, and it cannot complete a series of important functions such as kidney secretion, metabolism and maintaining internal balance. Therefore, the quality of life of dialysis patients is not high. Kidney transplantation is a complete renal function replacement, and its annual mortality is lower than that of dialysis patients [1]. However, due to the shortage of kidney donors, side effects of immunosuppressants and surgical complications, the development of kidney transplantation is limited [2]. Stem cells can form primitive cells of various tissues and organs of the human body. In the repair of kidney diseases, stem cells can differentiate into kidney cells and participate in the repair and kidney regeneration after kidney injury [3].
1 research background of stem cells
Stem cells have self-renewal ability and multi-directional differentiation potential, and can be divided into embryonic stem cells and adult stem cells according to their sources. The earliest stem cell research can be traced back to the 1960s. 1957, Nieman tried to transplant normal bone marrow into patients to treat hematopoietic dysfunction. In recent years, the great progress of induced pluripotent stem cells has further pushed stem cell research to the forefront of biomedical field, making it occupy an important position in medical and health, science and technology industry, national defense and other fields [6]. In clinical application, hematopoietic stem cells and mesenchymal stem cells are new medical technologies, which have achieved good results in the treatment of hematological diseases, autoimmune diseases, ischemic diseases of lower limbs, diabetes, nervous system diseases, malignant tumors and other diseases.
Mechanism of stem cells treating kidney diseases The physiological function of kidney is completed by various kidney cells. Glomerular endothelial cells, visceral epithelial cells and glomerular basement membrane are isomorphic to form the filtration membrane of the kidney, which plays a role in filtering plasma. The function of renal tubular reabsorption and secretion is mainly accomplished by renal tubular epithelial cells. At the same time, the cells with endocrine function in the kidney secrete a variety of active substances, which regulate the blood flow and water and salt metabolism of the kidney. Kidney disease is a comprehensive reaction of cytopathy, and all kinds of kidney diseases are closely related to the structural and functional changes of various kidney cells. The most fundamental thing to treat various renal diseases is to restore the quantity and quality of renal functional cells [7]. Stem cells can restore various physiological functions of the kidney by repairing and regenerating various renal parenchymal cells at the cellular level. The possible mechanisms of stem cells in treating kidney diseases are: differentiation into mesangial cells, endothelial cells, podocytes, renal tubular epithelial cells and so on. , repair various kidney injuries, promote kidney secretion, reduce the inflammatory reaction of damaged kidneys, and play an important role in the later stage of kidney repair [8].
Application of stem cells in the treatment of renal diseases
3. 1 stem cells for treating diabetes
Preparation of islet cells by stem cell technology and cell transplantation have become one of the effective methods to treat diabetes in the future. Transplantation of hematopoietic stem cells and mesenchymal stem cells has a good clinical application prospect in the treatment of diabetes. Huang et al. [9] made a beneficial exploration in the treatment of type I diabetes by autologous bone marrow hematopoietic stem cell transplantation, and improved the foreign research scheme, expanded the definition value of course screening, and improved the way of hematopoietic stem cell transfusion. For patients with a course of more than 2 months, reinfusion of splenic artery or pancreatic artery was used to increase the concentration of stem cells in the local pancreatic tissue of patients and improve the differentiation rate to islet cells, thus improving the clinical efficacy.
Researchers used human bone marrow mesenchymal stem cells to repair the damaged islets and glomeruli of diabetic mice, and found that human bone marrow mesenchymal stem cells can be located in the damaged pancreas and kidney of mice, improve the function of pancreatic β cells, promote insulin secretion, and effectively alleviate hyperglycemia. Some human bone marrow mesenchymal stem cells differentiate into glomerular epithelial cells in kidney, which can repair damaged kidney and improve renal function.
3.2 Stem Cell Therapy for Glomerular Diseases
In glomerular diseases, the damage of glomerular cells is irreversible and can lead to chronic renal failure. Studies have shown that stem cells can differentiate into mesangial cells, and it is feasible to repair glomerulus with MSCs. The key of cell therapy to improve nephropathy is that MSCs return to the damaged part of glomerular tissue, slow down the development of glomerulonephritis, help to repair glomerular basement membrane, including endothelium, stroma, epithelium and mesangium, and promote the proliferation of glomerular cells [12]. The glomerular membrane progenitor cells outside the glomerulus also promote glomerular repair. Imasawa et al. [13] confirmed that bone marrow-derived stem cells can differentiate into mesangial cells, participate in the renewal of glomerular endothelium and mesangial cells, repair microvessels, provide a new vision for the pathogenesis of nephropathy, and show great potential for stem cell therapy.
3.3 Stem cells in the treatment of hereditary nephropathy
Hereditary progressive nephritis is a kind of hereditary kidney disease that has appeared since childhood. Its clinical features are hematuria, auditory deafness and progressive renal insufficiency, which is the second largest genetic cause of renal failure. Traditional treatment mostly adopts drug intervention, renal replacement therapy and gene therapy, but there are some disadvantages such as long-term dependence on drug therapy and lack of evidence-based medical evidence, and renal replacement therapy usually makes the probability of renal insufficiency after transplantation higher. Stem cells have the advantages of strong self-appreciation ability and stable biological characteristics, and stem cell therapy provides a new treatment approach for modern medicine.
3.4 Stem cell therapy for nephrotic syndrome
Nephrotic syndrome is caused by many reasons, especially glomerular diseases such as increased glomerular basement membrane permeability and decreased glomerular filtration rate. There are four clinical characteristics: ① A large amount of proteinuria exceeds 3.5 g/d, which may lead to hyperlipidemia; ② Serum albumin with hypoalbuminemia < 30g/L; ③ Hyperlipidemia; ④ Edema can be divided into three categories according to the etiology and pathology, namely primary nephrotic syndrome, congenital nephrotic syndrome and secondary nephrotic syndrome [16]. Stem cell transplantation for nephrotic syndrome can effectively prevent the deterioration of renal function, eliminate clinical symptoms such as proteinuria, hematuria and edema, and restore normal renal function. Imai et al [18] used transplantation to treat nephrotic syndrome in rats. Peripheral vein infusion of rat bone marrow mesenchymal stem cells can effectively reduce urine protein, increase plasma protein level, improve lipid metabolism, protect renal function in model rats and promote the repair of renal pathological injury, which confirmed that stem cell transplantation has obvious therapeutic effect on nephrotic syndrome in rats.
Using stem cells to reconstruct damaged organs or tissues has opened a window for the development of regenerative medicine and tissue engineering. With the deepening of stem cell research technology and application level, new progress will be made in the study of stem cell differentiation into kidney cells, and stem cell transplantation will have a broader application prospect in the treatment of kidney diseases.
3.5 Stem Cell Therapy for Renal Failure
Chronic renal failure (CRF) is a clinical syndrome caused by many reasons, such as renal damage and progressive deterioration, serious damage to nephron and irreversible damage to renal parenchyma, which leads to excretion of metabolic waste and regulation of water, electrolyte and acid-base balance disorder. The main pathological manifestations are glomerulosclerosis, fibrosis, tubular atrophy, interstitial fibrous tissue hyperplasia and inflammatory cell infiltration. The main pathological manifestation of acute renal failure is acute tubular necrosis [19]. Kale et al [20] transplanted bone marrow stem cells into renal model mice with ischemia-reperfusion injury and found that the transplanted bone marrow stem cells were nephrophilic. After being implanted into the damaged kidney, it can differentiate into renal tubular epithelial cells, improve the structure and function of the kidney, a large number of necrotic renal tubular epithelial cells can be quickly replenished, and the plasma urea nitrogen level of mice is reduced. Renal progenitor cells start the repair process in the recovery period of ARF, the damaged/dead cells are removed, and the stem cells migrate to the necrotic area, which can differentiate into endothelial cells, providing early protection for ischemic ARF mice.
Using stem cells to reconstruct damaged organs or tissues has opened a window for the development of regenerative medicine and tissue engineering. With the deepening of stem cell research technology and application level, new progress will be made in the study of stem cell differentiation into kidney cells, and stem cell transplantation will have a broader application prospect in the treatment of kidney diseases.