Therapeutic Plasticity of Neural Stem Cells

Abstract

Neural stem cells (NSCs) have garnered significant scientific and commercial interest in the last 15 years. Given their plasticity, defined as the ability to develop into different phenotypes inside and outside of the nervous system, with a capacity of almost unlimited self-renewal, of releasing trophic and immunomodulatory factors, and of exploiting temporal and spatial dynamics, NSCs have been proposed for (i) neurotoxicity testing;(ii) cellular therapies to treat CNS diseases; (iii) neural tissue engineering and repair; (iv) drug target validation and testing; (v) personalized medicine. Moreover, given the growing interest in developing cell-based therapies to target neurodegenerative diseases, recent progress in developing NSCs from human-induced pluripotent stem cells has produced an analog of endogenous NSCs. Herein, we will review the current understanding on emerging conceptual and technological topics in the neural stem cell field, such as deep characterization of the human compartment, single-cell spatial-temporal dynamics, reprogramming from somatic cells, and NSC manipulation and monitoring. Together, these aspects contribute to further disentangling NSC plasticity to better exploit the potential of those cells, which, in the future, might offer new strategies for brain therapies.

Cell motility and migration as determinants of stem cell efficacy

“…Of all cell types, MSC and NSC are the most commonly used in preclinical and clinical trials in oncologic and degenerative diseases of the brain [18] , [19] , [20] , [21] . Hence, they were our first choice to test the existence of subpopulations with high migratory properties.…”

Momordica charantia polysaccharides modulate the differentiation of neural stem cells via SIRT1/Β-catenin axis in cerebral ischemia/reperfusion

“…In latest years, therapeutic ability of NSCs has been matter of intense research, fueled by the hope of exploiting their regenerative potential for the treatment of different kinds of neurological impairments [41,42]. Adult neurogenesis is the process whereby NSCs mature, migrate, and functionally integrate into the pre-existing neuronal network of an adult brain.…”

Combined Cell Therapy in the Treatment of Neurological Disorders

“…Most probably, this could be the result of the neurovascular niche restoration and formation of the optimum microenvironment [ 23 , 82 ] combined with the neuroprotective and neuroregenerative effects of OEC [ 83 , 84 ]. Better engraftment of NSC/NPC may promote functional recovery through direct cellular replacement mechanism [ 85 , 86 ] or the induction of repair mechanisms mediated by the paracrine delivery of trophic factors, immunomodulation, stimulation of neurogenesis and angiogenesis, and enhancement of neuroplasticity (well reviewed in [ 5 ]). NSC/NPC demonstrate paracrine activity of their own, and it can be combined with paracrine effects of other cell types, for example MSC [ 24 ].…”