## 2 Stem Cells and their Therapeutic Significance
### Stem-Cell Types in Regenerative Therapy  
Various cells can be considered in tissue engineering, stem or modified cells to replace lost neurons and somatic cells due to their neuroprotective potential. In order to develop safe and effective cell therapy methods that can be translated to clinical applications, it is important to understand the inherent characteristics of these potent cells; for instance, their engraftment, distribution pattern, differentiation and survival rate. Moreover, recognition of the differentiation process of stem cells is critical to enhance the treatment success of neurological diseases such as AD and PD. Finding the stem-cell \"niche\", the specific microenvironment of stem-cell generation, is an important factor in order to utilize the regenerative potential of these cells for treatment of neurodegenerative diseases [30]. The recognition of the NSC and their potential for neurogenesis has attracted researchers to assess the feasibility of their application in treatment of neurodegenerative diseases. NSCs have the ability to self-renew and generate multiple neural lineages, e.g., axonal regrowth or cell replacement [31]. They are able to differentiate into the three main cell types present in the central nervous system: neurons, astrocytes and oligodendrocytes [30]. Recently, numerus studies have been focused on stem-cell based therapies as promising solutions for treatment of CNS-related diseases and disorders [32]. Currently, for neurological repair therapy the main used stem cells are comprised of NSCs, neuroprotective stem cells, induced pluripotent stem cell (iPS cells), mesenchymal stem cells (MSC) and embryonic stem cells (ESC). The efficacy of differentiation of stem cells can be also improved genetically for transfer of new genes to induce better differentiation into neural lineages or to secrete defined therapeutic compounds (Figure 2) [32]. Some researchers have selected the iPSs as the most promising autologous source of stem cells which can be generated by genetic reprogramming of transcription factors of autologous somatic cells (e.g., fibroblasts). Novel gene editing techniques have been used for generating genetically corrected lines from patient derived iPSCs and/or for induction of mutations in control cell lines. They have attracted the attention of researchers for their apparent similarity to ESCs; while iPSCs grafts avoid the ethical issues intrinsic to human ESC work. The iPSCs are derived from individual patients, so they can be used for modeling diseases on a patient-by-patient basis. This makes the opportunity of screening the genomic variations among individuals that may aid in early diagnosis and preventing the progression of disease and also can be effective in finding the most appropriate pharmacological compounds for each individual. The striatal neuros derived from iPSCs obtained from [PERSON]'s disease (HD) patients, provided an in vitro disease model of HD [34]. The unilateral transplantation of syngeneic somatic NSCs within the substantia nigra pars compacta (SNPs) of aged PD mice revealed a considerable ability of grafted NSCs to fix nigrostriatal functionality [35]. In another study, to investigate the effectiveness of NSC transplantation, the NSCs  
Figure 2: Strategies and innovations to get better outcomes in treatment of neurodegenerative disease by stem-cell therapy. In addition to other drug or treatment, approaches could be used innate trophic actions of stem cells. Furthermore, stem cells could be genetically engineered to secret a specific therapeutic factor into site of neural damage by a novel carrier system like a cartridge. The engineered cells could deliver new therapeutic genes, differentiation induction genes or migration-induced gene or a missing/disease-relevant gene product. Adapted with permission from [33], [PERSON] et al., 2016.  
were isolated from postnatal day 14 mice and transplanted to the hippocampus in the mouse AD model.