Adult Neural Stem Cells: Basic Research and Production Strategies for Neurorestorative Therapy

Abstract

Over many decades, constructing genetically and phenotypically stable lines of neural stem cells (NSC) for clinical purposes with the aim of restoring irreversibly lost functions of nervous tissue has been one of the major goals for multiple research groups. The unique ability of stem cells to maintain their own pluripotent state even in the adult body has made them into the choice object of study. With the development of the technology for induced pluripotent stem cells (iPSCs) and direct transdifferentiation of somatic cells into the desired cell type, the initial research approaches based on the use of allogeneic NSCs from embryonic or fetal nervous tissue are gradually becoming a thing of the past. This review deals with basic molecular mechanisms for maintaining the pluripotent state of embryonic/induced stem and reprogrammed somatic cells, as well as with currently existing reprogramming strategies. The focus is on performing direct reprogramming while bypassing the stage of iPSCs which is known for genetic instability and an increased risk of tumorigenesis. A detailed description of various protocols for obtaining reprogrammed neural cells used in the therapy of the nervous system pathology is also provided.

Expression of genes involved in neurogenesis, and neuronal precursor cell proliferation and development: Novel pathways of human ovarian granulosa cell differentiation and transdifferentiation capability in�vitro

“…in the present study, a group of genes responsible for processes associated with neurogenesis, nervous system development and neural precursor cell proliferation were selected for analysis during long-term in vitro culture of Gcs. The results indicated that these cells have the potential to differentiate towards neurons, as they express neural-differentiation specific genes, providing further proof for their stem-like potential (14,20). a number of studies have reported that it is possible to obtain neuronal-like cells during the differentiation/transdifferentiation of other cell types (5,39,43,52).…”

“…in recent years, a number of attempts have been made to differentiate cells of stem-like potential towards neural lineage (5). These studies primarily used induced pluripotent stem cells (iPScs) (12)(13)(14). Despite the difficulties, an increasing number of scientists are trying to find more sources of functional nerve cells (15)(16)(17)(18).…”

“…Herman et al (20) was the first to present six protocols describing the reprogramming of bone marrow-derived human mesenchymal stem cells into neural stem cells. The process of this differentiation was possible by adding appropriate growth factors including brain-derived neurotrophic factor, platelet-derived growth factor, epidermal growth factor, fibroblast growth factor 2 and retinoic acid to the culture medium (14,20). another important model for obtaining neuronal cells is the transdifferentiation of somatic cells.…”

CD271+ stem cell treatment of patients with chronic stroke

“…A multitude of intertwined factors are acting in concert and influencing stem cell multiplication and differentiation; they can be grouped in signaling pathways based on respective sequences and roles: pro-multiplication-Jak/Stat, modulated by cytokines such as G-CSF interferons, granulocyte colony-stimulating factor (G-CSF), and interleukins (IL-6 and IL-10); Sonic Hedgehog (SHh) and Notch Signaling Pathways, important in proliferation and differentiation of neural stem cells; Wnt/β-catenin, important in embryonic development and tumorigenesis in adult tissues, and PI3K/Akt which is intertwined with the MAPK/ERK path via protein kinase B (Akt-1) which blocks apoptosis; and pro-differentiation: MAPK/ERK; activated through tyrosine kinase and G-protein receptors, and extracellular effectors such as EGF and FGF; and the TGF-β signaling pathway which activates apoptosis; finally at epigenetic levels important roles are held by demethylases (ex ascorbic acid) and histone deacetylases (ex valproic acid) ( 56 ).…”

Cell Signaling in Neuronal Stem Cells

“…The TET1-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine is important for the demethylation of DNA in mammalian cells [ 85 ]. Interestingly, the demethylation induced by neuronal activity of the brain-derived neurotrophic factor (BDNF) and FGF promoters was completely abolished in the adult DG after the overexpression of short hairpin RNA (shRNA) against TET1 in vivo, suggesting an important role for TET1 in the regulation of neurogenesis induced by activity in the adult hippocampus [ 86 ].…”