Abstract
The ability of mammalian neural stem cells (NSCs) to self-renew and differentiate throughout adulthood has made them ideal to study neurogenesis and attractive candidates for neurodegenerative disease therapies. In the adult mammalian brain, NSCs are maintained in the neurovascular niche (NVN) where they are found near the specialized blood vessels, suggesting that brain endothelial cells (BECs) are prominent orchestrators of NSC fate. However, most of the current knowledge of the mammalian NVN has been deduced from nonhuman studies. To circumvent the challenges of in vivo studies, in vitro models have been developed to better understand the reciprocal cellular mechanisms of human NSCs and BECs. This review will cover the current understanding of mammalian NVN biology, the effects of endothelial cell-derived signals on NSC fate, and the in vitro models developed to study the interactions between NSCs and BECs.
Highlights
It was previously believed that mammalian neurogenesis occurred exclusively during embryonic development
In the adult mammalian brain, neural stem cells (NSCs) are maintained in the neurovascular niche (NVN) where they are found near the specialized blood vessels, suggesting that brain endothelial cells (BECs) are prominent orchestrators of NSC fate
Endothelial cells employ multiple mechanisms to influence other cell types: (1) juxtacrine signaling with adjacent cells using cell membrane and extracellular matrix (ECM) proteins; (2) paracrine signaling with proximal cells using diffusible growth factors; and (3) endocrine signaling with distant cells using hormones released into the circulatory system
Summary
It was previously believed that mammalian neurogenesis occurred exclusively during embryonic development. Given their similarities and lack of established definitions, populations of NSCs and NPCs (NSCs/NPCs) are often described and studied together.[4,5] The innate abilities of NSCs/ NPCs have led to scientific investigations to elucidate the underlying cellular mechanisms that govern their cell fate This is of particular clinical relevance to cell-replacement therapies for neurodegenerative diseases to replace dead or damaged neural cells.[6,7] Understanding how NSCs behave in the adult mammalian brain will accelerate the successful clinical application of NSCs in patients with neurodegenerative diseases. NSCs/NPCs will be imperative for the optimal expansion and differentiation of NSC populations and potential clinical translations.[19,20] In this review, we will illustrate the current understanding of mammalian NVN biology, identify the vascular contributions that govern NSC/ NPC behavior, and evaluate the past and current in vitro systems developed to recapitulate and study these cellular interactions
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