Abstract
Neural stem cells represent an attractive tool for the development of regenerative therapies and are being tested in clinical trials for several neurological disorders. Human neural stem cells can be isolated from the central nervous system or can be derived in vitro from pluripotent stem cells. Embryonic sources are ethically controversial and other sources are less well characterized and/or inefficient. Recently, isolation of NSC from the cerebrospinal fluid of patients with spina bifida and with intracerebroventricular hemorrhage has been reported. Direct reprogramming may become another alternative if genetic and phenotypic stability of the reprogrammed cells is ensured. Here, we discuss the advantages and disadvantages of available sources of neural stem cells for the production of cell-based therapies for clinical applications. We review available safety and efficacy clinical data and discuss scalability and quality control considerations for manufacturing clinical grade cell products for successful clinical application.
Highlights
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Neither have we included Neural stem cells (NSC) from the peripheral nervous system (PNS) that can be isolated from intestine, skin, olfactory bulb, and other tissues, because these are derived from the neural crest, express different markers, and generate a different progeny, including mesenchymal derivatives, and, represent a markedly different subtype of NSC [11]
In contrast with early transplantation trials, in which fetal central nervous system (CNS) tissue was transplanted into the patient soon after dissection to ensure viability, the optimization of in vitro culture of fetal NSC (fNSC) has solved many of the major supply and logistic hurdles of using fresh tissue [15,16]
Summary
Neural stem cells (NSC) are self-renewing, multipotent cells that generate neurons and glial cells during development and maintain brain homeostasis. Similar to mesenchymal stem cells (MSC), NSC can exert immunomodulatory effects and transplantation of NSC has been shown to inhibit T-cell proliferation. All these properties make NSC attractive for regenerative therapies, in particular considering the limited capacity for self-repair and the lack of effective therapies for most disorders of the central nervous system (CNS) [1,2,3]. Neither have we included NSC from the peripheral nervous system (PNS) that can be isolated from intestine, skin, olfactory bulb, and other tissues, because these are derived from the neural crest, express different markers, and generate a different progeny, including mesenchymal derivatives, and, represent a markedly different subtype of NSC [11]
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