PMID- 30565961 OWN - NLM STAT- MEDLINE DCOM- 20200310 LR - 20200310 IS - 1559-7016 (Electronic) IS - 0271-678X (Print) IS - 0271-678X (Linking) VI - 39 IP - 3 DP - 2019 Mar TI - A silicon nanomembrane platform for the visualization of immune cell trafficking across the human blood-brain barrier under flow. PG - 395-410 LID - 10.1177/0271678X18820584 [doi] AB - Here we report on the development of a breakthrough microfluidic human in vitro cerebrovascular barrier (CVB) model featuring stem cell-derived brain-like endothelial cells (BLECs) and nanoporous silicon nitride (NPN) membranes (microSiM-CVB). The nanoscale thinness of NPN membranes combined with their high permeability and optical transparency makes them an ideal scaffold for the assembly of an in vitro microfluidic model of the blood-brain barrier (BBB) featuring cellular elements of the neurovascular unit (NVU). Dual-chamber devices divided by NPN membranes yield tight barrier properties in BLECs and allow an abluminal pericyte-co-culture to be replaced with pericyte-conditioned media. With the benefit of physiological flow and superior imaging quality, the microSiM-CVB platform captures each phase of the multi-step T-cell migration across the BBB in live cell imaging. The small volume of <100 microL of the microSiM-CVB will enable in vitro investigations of rare patient-derived immune cells with the human BBB. The microSiM-CVB is a breakthrough in vitro human BBB model to enable live and high-quality imaging of human immune cell interactions with the BBB under physiological flow. We expect it to become a valuable new tool for the study of cerebrovascular pathologies ranging from neuroinflammation to metastatic cancer. FAU - Mossu, Adrien AU - Mossu A AUID- ORCID: 0000-0001-5986-2762 AD - 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland. FAU - Rosito, Maria AU - Rosito M AD - 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland. FAU - Khire, Tejas AU - Khire T AD - 2 Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA. FAU - Li Chung, Hung AU - Li Chung H AD - 2 Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA. FAU - Nishihara, Hideaki AU - Nishihara H AD - 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland. FAU - Gruber, Isabelle AU - Gruber I AD - 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland. FAU - Luke, Emma AU - Luke E AD - 2 Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA. FAU - Dehouck, Lucie AU - Dehouck L AD - 3 Blood Brain Barrier Laboratory, University of Artois, Lens, France. FAU - Sallusto, Federica AU - Sallusto F AD - 4 Institute for Research in Biomedicine, Universita della Svizzera Italiana, Bellinzona, Switzerland. AD - 5 Institute for Microbiology, ETH Zurich, Zurich, Switzerland. FAU - Gosselet, Fabien AU - Gosselet F AD - 3 Blood Brain Barrier Laboratory, University of Artois, Lens, France. FAU - McGrath, James L AU - McGrath JL AD - 2 Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA. FAU - Engelhardt, Britta AU - Engelhardt B AD - 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland. LA - eng GR - R01 HL125265/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20181219 PL - United States TA - J Cereb Blood Flow Metab JT - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JID - 8112566 RN - 0 (Membranes, Artificial) RN - 0 (Silicon Compounds) RN - QHB8T06IDK (silicon nitride) SB - IM MH - Blood-Brain Barrier/*metabolism MH - *Cell Movement MH - Coculture Techniques MH - Endothelial Cells/cytology MH - Humans MH - Immune System/*cytology MH - *Membranes, Artificial MH - Microfluidics/instrumentation/*methods MH - *Models, Biological MH - Nanotechnology/methods MH - Pericytes/cytology MH - Permeability MH - Silicon Compounds PMC - PMC6421249 OTO - NOTNLM OT - Blood-brain barrier OT - T-cell migration OT - microfluidics OT - nanoporous silicon nitride membrane OT - two-compartmental flow chamber EDAT- 2018/12/20 06:00 MHDA- 2020/03/11 06:00 PMCR- 2020/03/01 CRDT- 2018/12/20 06:00 PHST- 2018/12/20 06:00 [pubmed] PHST- 2020/03/11 06:00 [medline] PHST- 2018/12/20 06:00 [entrez] PHST- 2020/03/01 00:00 [pmc-release] AID - 10.1177_0271678X18820584 [pii] AID - 10.1177/0271678X18820584 [doi] PST - ppublish SO - J Cereb Blood Flow Metab. 2019 Mar;39(3):395-410. doi: 10.1177/0271678X18820584. Epub 2018 Dec 19.