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.
Highlights
The concept of the stem cell niche was officially used for the first time by Schofield [1] in 1978 to define local environments with specific molecular and cellular characteristics that are required for the maintenance of hematopoietic stem cells
The assay to test in vitro neural stem/progenitor cell (NPC)-self-renewal and multi-potency consisted of assessing their ability to give rise to neurospheres [4]
To the hematopoietic niche and obviously in addition to the intrinsic and specific characteristics of neural stem cells, the fate of NPCs and their self-renewal and differentiation capacity are tightly regulated by complex interactions between intrinsic and extrinsic signals provided by surrounding cells in the niche and by distant sources [7]
Summary
The concept of the stem cell niche was officially used for the first time by Schofield [1] in 1978 to define local environments with specific molecular and cellular characteristics that are required for the maintenance of hematopoietic stem cells. NPCs, upon interaction with CNS-resident cells, start releasing neurotrophic factors, such as Nerve Growth Factor-NGF, BDNF, and Glial Derived Neurotrophic Factor-GDNF, along with reactive species, binding proteins, purines, or cytokines that might significantly reduce scar formation and/or increase the survival and function of endogenous glial and neuronal progenitors This was originally demonstrated in mice with primary inflammatory disorders, including the animal model of MS [173, 181] or stroke [182, 183] and in mice with neurodegenerative diseases mediated by reactive inflammation, such as Parkinson’s Disease [184]. Intracerebral Transplantation of Neural Stem Cells for the Treatment of Ischemic Stroke
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