Seo, Suyeong Choi, Chi-Hoon Yi, Kyung Sik Kim, Seung U. Lee, Kangwon Choi, Nakwon Lee, Hong Jun Cha, Sang-Hoon Kim, Hong Nam 2024-01-19T14:31:04Z 2024-01-19T14:31:04Z 2021-09-04 2021-07 1758-5082 https://pubs.kist.re.kr/handle/201004/116830 The neurovascular unit (NVU) comprises multiple types of brain cells, including brain endothelial cells, astrocytes, pericytes, neurons, microglia, and oligodendrocytes. Each cell type contributes to the maintenance of the molecular transport barrier and brain tissue homeostasis. Several disorders and diseases of the central nervous system, including neuroinflammation, Alzheimer's disease, stroke, and multiple sclerosis, have been associated with dysfunction of the NVU. As a result, there has been increased demand for the development of NVU in vitro models. Here, we present a three-dimensional (3D) immortalized human cell-based NVU model generated by organizing the brain microvasculature in a collagen matrix embedded with six different types of cells that comprise the NVU. By surrounding a perfusable brain endothelium with six types of NVU-composing cells, we demonstrated a significant impact of the 3D co-culture on the maturation of barrier function, which is supported by cytokines secreted from NVU-composing cells. Furthermore, NVU-composing cells alleviated the inflammatory responses induced by lipopolysaccharides. Our human cell-based NVU in vitro model could enable elucidation of both physiological and pathological mechanisms in the human brain and evaluation of safety and efficacy in the context of high-content analysis during the process of drug development. English IOP PUBLISHING LTD An engineered neurovascular unit for modeling neuroinflammation Article 10.1088/1758-5090/abf741 1 BIOFABRICATION, v.13, no.3 BIOFABRICATION 13 3 scie scopus 000647654900001 2-s2.0-85105824359 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article neurovascular unit blood-brain barrier co-culture in vitro model vascular permeability neuroinflammation