title: Reconstituting vascular microenvironment of neural stem cell niche in three-dimensional extracellular matrix.
abstract: Neural stem cells (NSCs) reside in a vascular microenvironment termed the "NSC niche." Blood vessels in the NSC niche play an important role in maintaining an appropriate balance between NSC self-renewal and differentiation that serves to maintain homeostasis. Understanding the role of brain vessels in the NSC niche will facilitate basic research in neurogenesis and vasculogenesis as well as aid the development of potential therapies for degenerative disorders. Here, an in vitro-reconstituted NSC-vascular niche consisting of a 3D brain vasculature and extracellular matrix (ECM) microenvironment that allows NSCs to adopt physiologically relevant phenotypes through the combined effects of ECM components, chemical gradients, and signaling effectors from the brain vasculature is described. The reconstituted niche can provide precise spatiotemporal control of the NSC niche, regulating self-renewal, proliferation and colony formation of NSCs, and suppressing neuronal generation but promoting NSC differentiation into astrocytes and oligodendrocytes. It is proved that Notch effectors regulate both the astrocyte differentiation and NSC self-renewal, but the astrocyte differentiation is more active in NSCs in close proximity to brain vasculature. A potential role of the other vascular microenvironmental factor of pigment epithelium-derived factor from brain vasculature in the regulation of NSC self-renewal is also proved.
authors: Department of Mechanical Engineering, Korea University, #512B, Innovation Hall, Anam, Seongbuk, Seoul, 136-713, South Korea.
authors: Yoojin
authors: Y
authors: Shin
authors: Kisuk
authors: K
authors: Yang
authors: Sewoon
authors: S
authors: Han
authors: Hyun-Ji
authors: HJ
authors: Park
authors: Yun
authors: Y
authors: Seok Heo
authors: Seung-Woo
authors: SW
authors: Cho
authors: Seok
authors: S
authors: Chung
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D001921:Brain / Q000098:blood supply; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D046210:Microfluidic Analytical Techniques; D055806:Microvessels / Q000502:physiology; D008954:Models, Biological; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D055153:Stem Cell Niche / Q000502:physiology*
chemical_list: D001672:Biocompatible Materials; D016326:Extracellular Matrix Proteins
keywords: differentiation; microfluidic systems; neural stem cells; niche; self-renewal