Research Area

Neural Stem Cells


Overview of Neural Stem Cells

Neural Stem Cells

Neural stem cells (NSCs) are those that exist in the nervous system and have the potential to differentiate into neuronal neurons, astrocytes, and oligodendrocytes, which can produce a large amount of brain tissue and can self-renew, and a population of cells sufficient to provide a large number of brain tissue cells. Neural stem cells are self-renewing, multipotent cells that generate the neurons and glia of the nervous system of all animals during embryonic development. Some neural stem cells persist in the adult vertebrate brain and continue to produce neurons throughout life. Stem cells are characterized by their capacity to differentiate into multiple cell types. They undergo symmetric or asymmetric cell division into two daughter cells. In symmetric cell division, both daughter cells are also stem cells. In asymmetric division, a stem cells produces one stem cell and one specialized cell. In should be emphasized that in all neural tissues such as the cerebrospinal and spinal cord, different types of progeny cells and different distributions.

Classification of Neural Stem Cells

According to the differentiation potential and the production of daughter cell types can be divided into four categories. (1) The neural tube epithelial cells have the strongest ability to divide, and only exist in the embryonic stage, which can produce radial glial neurons and neuroblasts. (2) Radial glial neurons can divide themselves to produce neuronal precursor cells or glial cells at the same time. The main function is to produce projection neurons in the brain during childhood development to complete the basic nervous tissue cells in the cortex and nucleus of the brain. (3) Neuroblasts, the main neural stem cells in adults, have the ability to divide and produce neural precursor cells and neurons and various glial cells. (4) Neural precursor cell, precursor cells of various types of nerve cells, such as microglia, are produced by glial cell precursors. In addition, we can also classify according to where the neural stem cells are located. It can be divided into neural crest stem cells (NC-SC) and central nervous stem cells (CNS-SC).

The division pattern of neural stem cells

Figure 1. The division pattern of neural stem cells

Application of Neural Stem Cells

Neural stem cells play an important role in neural development and repair of damaged nerve tissue. Neural stem cell transplantation is an effective method to repair and replace damaged brain tissue, and can reconstruct part of the loop and function. Besides, neural stem cells can be used as gene carriers for gene therapy of intracranial tumors and other neurological diseases, and use neural stem cells as gene therapy vectors to make up for some of the shortcoming of viral vectors. Wagner et al. transplanted neural stem cells into the rat brain of the Parkinson’s disease model. The neural stem cells migrated in the brain tissue and repaired the damaged brain tissue, and the symptoms of tremor were significantly alleviated. It may be that the neural stem cells differentiate into dopaminergic neurons for therapeutic purposes. Neuronal cells isolated from aborted fetal brain by Piccini et al, transplantation into the brain of patients to treat Parkinson’s disease results in more than half of the patients’ symptoms being significantly improved and the effect persists. Multiple sclerosis is a highly morbid neurological disease in which the myelin-derived oligodendrocytes are found to be destroyed or lose function I their rodent model, transplanted neural stem cells directly into the rat brain, and the transplanted cells migrated extensively in the brain. In the differentiated oligodendrocytes, about 40% of the cells from myelin, and their characteristics are very close to normal, and the typical symptoms of some transplanted animals are also significantly improved. Gliomas are one of the difficult points in medical treatment. It is difficult to remove tumors by surgery, and it is easy to relapse, radiotherapy and chemotherapy have certain effects on tumors. Since neural stem cells have a migration function, this property can be used to release drugs to the brain. Transgenic treatment of murine neural stem cells to secrete IL-4, which activates the immune system and attacks tumor cells against tumors. After the injection of this cell, the experimental mice with gliomas have a much longer lifespan than the untreated rats. Magnetic resonance imaging showed that the large tumors in the brain of the rats showed signs of shrinking. Interestingly, even if the injected neural stem cells did not secrete IL-4, the lifespan of the experimental mice was prolonged. Ling et al believe that this is because neural stem cells can also secrete an unknown substance that can slow the division of tumor cells. In addition, neural stem cells have certain practical value for judging drug efficacy and drug toxicity. For example, neural stem cell culture technology can be used to observe the neural activity of certain natural compounds and synthetic compounds, and provide a theoretical basis for the development of small molecules therapeutic drugs.

Obstacles to the Application of Neural Stem Cells

There are still many problems in the application of neural stem cells. Most of the established neural stem cell lines are derived from mice, and there are obvious species differences between mice and humans; insufficient source of neural stem cells; partially transplanted neural stem cells develop into brain tumors; the non-selective expression of neural stem cell transfection and the in situ regulation of transfection gene expression, the use of embryonic stem cells instead of neural stem cells have sociological and ethical problems. Not only above-mentioned problems, but also many difficulties in the neural stem cells have not been broken. For example: (1) the mechanism of proliferation, differentiation and migration of neural stem cells after transplantation has not been clearly explained, and the precise regulation of neural stem cells is still a long road; (2) in the selection of sources of neural stem cell transplantation, systematic comparison studies have not been made to determine the best source. (3) At present, most transplants are only in the experimental stage of animals, and there is still a greater risk of applying neural stem cell transplantation to clinical practice. However, looking at the current research situation, the prospects are still bright, and various potential problems have been gradually recognized and tried by researchers. It is believed that neural stem cells will eventually play a huge role in the treatment of central nervous system diseases.

References:

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  3. Gage FH. Mammalian neural stem cells. Science 2000, 287(5457): 1433-8.
  4. Temple S. Division and differentiation of isolated CNS blast cells in microculture. Nature. 1989, 340(6233): 471-3.
  5. Bergstrom, Forsbery-Nilsson. Neural stem cells: Brain building blocks and beyond. Upsala Journal of Medical Sciences. 117(2): 132-42
  6. Virginie bonnamain, Isabelle Neveu, Philippe Naveilhan. Neural stem/progenitor cells as promising candidates for regenerative therapy of the central nervous system. Cell Neurosci. 2012; 6:17.
  7. Kornack DR, Rakic P. Cell proliferation without neurogenesis in adult primate neocortex. Science. 2001, 294(5549): 2127-30.
  8. Czeisler Catherine, Short Aaron, Nelson Tyler et al. Surface topography during neural stem cell differentiation regulates cell migration and cell morphology. J. Comp. Neurol. 2016, 524(17): 3485-3502.

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