## 2 Stem Cells and their Therapeutic Significance
### Cell Therapy of Neural System Using Stem Cells  
The complex structure of the brain and central neural system make them more restricted to access and understand the mechanism of diseases related to these regions. Their successful treatment is not yet feasible and thus prevention and neuroprotection become more important than cure. Telomerase enzyme inside the cells have a protective function against neurons damage. Stem-cell therapy techniques have been recently developed; and similar to telomerase enzyme activity, have the ability of protection and maintenance of neuron function. [17]. For many years, it was believed that CNS tissue does not have the ability of renewal, but recent studies have challenged this dogma. Numerous experiments have been successfully carried out on the application of neural stem cells (NSC) or neural precursor cells (NPC) for transplantation therapy for CNS diseases. Throughout human life, like most other mammalian species, generation of new neurons through a process known as neurogenesis are carried out by NSCs. Generation of new neurons will occur in the subventricular zone (SVZ) of the lateral ventricles and they reach the olfactory bulb through the rostral migratory system. Simultaneously, movement of the new hippocampal granule neurons to  
Figure 1: Representative diagram depicting the main types and sources of stem cells and their potential to differentiate into various lineages. Adapted with permission from [22], [PERSON] et al., 2018.  
granule cell layer leads to formation of a chain network of migrating neuroblasts which eventually differentiate into various neural cells [16; 23]. In most known neurodegenerative diseases, neural cell structures are affected and eventually lose function. Therefore, successful regenerative therapy can be achieved by replacement of damaged neurons with the new ones or by restoration of neural tissue/organs [2]. The progress of cell therapy techniques in transplantation of stem cells has improved the shortage of neuron function in both acute and chronic neurodegenerative disorders. During the last few years, the advance in transplantation techniques of human or animal stem cells has expended much effort in preclinical brain research. This method also has the advantage of increasing the restorative response to CNS injury, which can be directly triggered by the stimulation of activated astrocytes. This response is believed to be mediated by different trophic and growth factors, such as nerve growth factor, brain-derived neurotrophic factor, vascular endothelial growth factor, fibroblast growth factor and erythropoietin. These factors can play neurotrophic roles for neural stem cells in vitro and can also retain neurogenesis in the adult CNS. Cell therapies have been developed to aid in CNS injuries, but to succeed in therapeutic approaches of stem cells therapy it is necessary to fully understand the physiological mechanism related to neurological diseases. Since current knowledge in neural development is incomplete, it is unclear whether these findings obtained in vitro can be operational for in vivo experiments or not. However, implantation of stem-cell scaffolds may induce a host tissue response. Encapsulation of stem cells can be a promising approach to minimize immune response and facilitate safety issues. Encapsulation can also promote the application of stem-cell therapies in clinical trials. Some preclinical reports demonstrated the feasibility and efficacy of microencapsulation methods for coating individual cells in AD models. For example, encapsulation of human mesenchymal stem cells with glycan-like peptide and their transplantation in an AD mouse model decreased amyloid deposition or suppression of glial and microglial responses [24]. Furthermore, other studies demonstrated the improvement of stem-cell survival and the cognitive abilities in AD mouse models using the encapsulation of neural stem cells (NSCs) within different types of hydrogels (e.g., dextran dialdehyde cross-linked with gelatin) [25; 26].