PMID- 33849004 OWN - NLM STAT- MEDLINE DCOM- 20211025 LR - 20211025 IS - 1758-5090 (Electronic) IS - 1758-5082 (Linking) VI - 13 IP - 3 DP - 2021 May 5 TI - An engineered neurovascular unit for modeling neuroinflammation. LID - 10.1088/1758-5090/abf741 [doi] AB - 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 NVUin vitromodels. 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 NVUin vitromodel 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. CI - (c) 2021 IOP Publishing Ltd. FAU - Seo, Suyeong AU - Seo S AD - Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea. AD - Program in Nano Science and Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea. AD - These authors contributed equally to this work. FAU - Choi, Chi-Hoon AU - Choi CH AD - Department of Radiology, Chung Buk National University Hospital, Cheongju, Chung Buk, Republic of Korea. AD - College of Medicine, Chung Buk National University, Cheongju, Chung Buk 28644, Republic of Korea. AD - These authors contributed equally to this work. FAU - Yi, Kyung Sik AU - Yi KS AD - Department of Radiology, Chung Buk National University Hospital, Cheongju, Chung Buk, Republic of Korea. FAU - Kim, Seung U AU - Kim SU AD - Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, BC, Canada. FAU - Lee, Kangwon AU - Lee K AD - Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea. FAU - Choi, Nakwon AU - Choi N AUID- ORCID: 0000-0003-2993-9233 AD - Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea. AD - Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea. AD - KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea. FAU - Lee, Hong Jun AU - Lee HJ AD - College of Medicine, Chung Buk National University, Cheongju, Chung Buk 28644, Republic of Korea. AD - Research Institute, eBiogen Inc., Seoul, Republic of Korea. FAU - Cha, Sang-Hoon AU - Cha SH AD - Department of Radiology, Chung Buk National University Hospital, Cheongju, Chung Buk, Republic of Korea. AD - College of Medicine, Chung Buk National University, Cheongju, Chung Buk 28644, Republic of Korea. FAU - Kim, Hong Nam AU - Kim HN AUID- ORCID: 0000-0002-0329-0029 AD - Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea. AD - Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210505 PL - England TA - Biofabrication JT - Biofabrication JID - 101521964 SB - IM MH - Astrocytes MH - *Blood-Brain Barrier MH - *Endothelial Cells MH - Humans MH - *Inflammation MH - *Neurons MH - Pericytes OTO - NOTNLM OT - blood-brain barrier OT - co-culture OT - in vitro model OT - neuroinflammation OT - neurovascular unit OT - vascular permeability EDAT- 2021/04/14 06:00 MHDA- 2021/10/26 06:00 CRDT- 2021/04/13 20:30 PHST- 2020/12/01 00:00 [received] PHST- 2021/04/13 00:00 [accepted] PHST- 2021/04/14 06:00 [pubmed] PHST- 2021/10/26 06:00 [medline] PHST- 2021/04/13 20:30 [entrez] AID - 10.1088/1758-5090/abf741 [doi] PST - epublish SO - Biofabrication. 2021 May 5;13(3). doi: 10.1088/1758-5090/abf741.