PMID- 34710793 OWN - NLM STAT- MEDLINE DCOM- 20211214 LR - 20211214 IS - 1878-5905 (Electronic) IS - 0142-9612 (Linking) VI - 279 DP - 2021 Dec TI - Human bone marrow-derived mesenchymal stem cells play a role as a vascular pericyte in the reconstruction of human BBB on the angiogenesis microfluidic chip. PG - 121210 LID - S0142-9612(21)00567-6 [pii] LID - 10.1016/j.biomaterials.2021.121210 [doi] AB - A blood-brain barrier (BBB) on a chip similar to the in vivo BBB is important for evaluating the efficacy of reparative cell therapeutics for ischemic stroke in vitro. In this study, we established human BBB-like microvasculature on an angiogenesis microfluidic chip and analyzed the role of human pericytes (hPCs) and human astrocytes (hACs) on the architecture of human brain microvascular endothelial cells (hBMEC)-derived microvasculature on a chip. We found that human bone marrow mesenchymal stem cells (hBM-MSCs) play a role as perivascular pericytes in tight BBB reformation with a better vessel-constrictive capacity than that of hPCs, providing evidence of reparative stem cells on BBB repair rather than a paracrine effect. We also demonstrated that pericytes play an important role in vessel constriction, and astrocytes may induce the maturation of a capillary network. Higher expression of VEGF, SDF-1alpha, PDGFRbeta, N-cadherin, and alpha-SMA in hBM-MSCs than in hPCs and their subsequent downregulation with hBMEC co-culture suggest that hBM-MSCs may be better recruited and engaged in the BBB-microvasculature than hPCs. Collectively, the human BBB on a chip may be adopted as an alternative to evaluate in vitro cellular behavior and the engagement of cell therapeutics in BBB regeneration and may also be used for studying stroke. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Kim, Sumin AU - Kim S AD - Department of Genetic Biotechnology, College of Life Science and Graduate School of Biotechnology, Kyung Hee University, Yong in, 17104, South Korea. FAU - Lee, Somin AU - Lee S AD - Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, 08826, South Korea. FAU - Lim, Jungeun AU - Lim J AD - Department of Mechanical Engineering, Seoul National University, Seoul, 08826, South Korea. FAU - Choi, Hyeri AU - Choi H AD - Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, 08826, South Korea. FAU - Kang, Habin AU - Kang H AD - Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, 08826, South Korea. FAU - Jeon, Noo Li AU - Jeon NL AD - Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, 08826, South Korea; Department of Mechanical Engineering, Seoul National University, Seoul, 08826, South Korea. FAU - Son, Youngsook AU - Son Y AD - Department of Genetic Biotechnology, College of Life Science and Graduate School of Biotechnology, Kyung Hee University, Yong in, 17104, South Korea; Kyung Hee Institute of Regenerative Medicine (KIRM), Medical Science Research Institute, Kyung Hee University Hospital, Seoul, 02447, South Korea. Electronic address: ysson@khu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211021 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 SB - IM MH - *Blood-Brain Barrier MH - Bone Marrow MH - Endothelial Cells MH - Humans MH - *Mesenchymal Stem Cells MH - Microfluidics MH - Pericytes OTO - NOTNLM OT - BBB-On-a-chip OT - BM-MSC OT - Blood-brain barrier OT - Microfluidic chip OT - Pericyte EDAT- 2021/10/29 06:00 MHDA- 2021/12/15 06:00 CRDT- 2021/10/28 20:27 PHST- 2021/01/06 00:00 [received] PHST- 2021/10/07 00:00 [revised] PHST- 2021/10/20 00:00 [accepted] PHST- 2021/10/29 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/10/28 20:27 [entrez] AID - S0142-9612(21)00567-6 [pii] AID - 10.1016/j.biomaterials.2021.121210 [doi] PST - ppublish SO - Biomaterials. 2021 Dec;279:121210. doi: 10.1016/j.biomaterials.2021.121210. Epub 2021 Oct 21.