神经元干细胞英文
What are Neural Stem Cells?
Neural stem cells, also known as neural progenitor cells (NPCs), are undifferentiated cells found in the central nervous system (CNS) that have the ability to differentiate into various neural cell types. NPCs, though not yet fully-characterized, hold significant promise in the advancement of treatment and understanding of several neurodegenerative disorders.
Types of Neural Stem Cells
There are mainly two types of neural stem cells:
- Embryonic Neural Stem Cells: These cells are found in the developing embryo and can differentiate into neurons, astrocytes, oligodendrocytes, and other specialized cell types that make up the nervous system.
- Adult Neural Stem Cells: These cells are found in adult CNS brain and spinal cord. They usually remain silent or dormant but can be activated to self-renew and differentiate into a range of neural cell types during injury or regeneration.
Discovering Neural Stem Cells
The first discovery of neural stem cells was made by Joseph Altman and Gopal Das in 1965. In their initial study, they noticed the presence of specific spheres of cells in the adult hippocampus of several small mammals that had the characteristics of stem cells. Later research has found NPCs in several other regions of the adult nervous system as well.
Further research revealed that NPCs could be isolated and expanded from embryonic and adult brains and neuronal tissues, which implied a significant potential for use in regenerative therapies. However, the final cell product would need to be purified and characterized to ensure safety and maximize efficacy before clinical trials could begin.
Understanding Neural Stem Cell Fate
Neural stem cells fate depends on various factors including the signals they receive, the microenvironment they reside in, and many intrinsic factors that drive differentiation or maintain self-renewal. Several transcriptional factors and signaling pathways such as Notch, Wnt, LIF, BMP, and SHH are known to be important regulators of NPC fate decisions.
Over recent years, researchers discovered that specific transcriptional factors such as Sox2, Pax6, and Olig2 play a significant role in determining the fates of NPCs. Interestingly, a combination of these factors can reprogram somatic cells into NPCs or other neural lineages, thus offering therapeutic potential in neurological diseases like Parkinsons disease and spinal cord injuries.
The Therapeutic Potential of Neural Stem Cells
Neural stem cells offer several therapeutic potentials:
- Cell replacement: Neural stem cells could differentiate into lost neuronal cell types in neurodegenerative diseases, such as Parkinsons or Alzheimers disease.
- Modulating Neural Activity: Neural stem cells could secrete paracrine factors that promote endogenous repair while reducing inflammation, a critical step in neuroprotection.
- Gene Editing: Neural stem cells can host genetic modification techniques like CRISPR, which could be used to correct defects in the genome associated with several neurological disorders.
Challenges in Neural Stem Cell Research
Although promising, research on neural stem cells faces several challenges both for research and clinical applications:
- Contamination: The final cell product may have remnants of other cell types from the extraction process, leading to unintended consequences after transplantation.
- Tumorigenicity: As NPCs are self-renewing cells, they could trigger the development of tumors if a mutation occurs during expansion.
- Efficient differentiation: Neural stem cells must have reproducible differentiation routes that deliver safe, effective, and consistent cell products.
- Immune rejection: Any cell transplantation runs the risk of immune rejection, which is especially significant for ESC or iPSC derived NPC transplantation which carries a risk of forming teratomas.
Conclusion
Neural stem cells are undifferentiated multipotent cells found in developing and adult nervous systems with the potential to differentiate into different neural cells. Researchers are investigating neural stem cells for their therapeutic potential in neurological disorders, including regenerating lost neurons, modulating neural activity, and genome editing. Researchers and clinicians face several challenges, including contamination, tumorigenicity, and immune rejection, that need to be overcome before these therapies can be mainstreamed.
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