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Park, Tae-Eun

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Tae-Eun

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Park, Tae-Eun

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2016 - 20202

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Author's Publications: search.filters.isAuthorOfPublication.69c5d1b9-e2e3-42df-bd1f-fb40c5627d0a

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    Distinct Contributions of Astrocytes and Pericytes to Neuroinflammation Identified in a 3D Human Blood-Brain Barrier on a Chip
    (Public Library of Science, 2016) Herland, Anna; van der Meer, Andries D.; FitzGerald, Edward A.; Park, Tae-Eun; Sleeboom, Jelle J. F.; Ingber, Donald
    Neurovascular inflammation is a major contributor to many neurological disorders, but modeling these processes in vitro has proven to be difficult. Here, we microengineered a three-dimensional (3D) model of the human blood-brain barrier (BBB) within a microfluidic chip by creating a cylindrical collagen gel containing a central hollow lumen inside a microchannel, culturing primary human brain microvascular endothelial cells on the gel’s inner surface, and flowing medium through the lumen. Studies were carried out with the engineered microvessel containing endothelium in the presence or absence of either primary human brain pericytes beneath the endothelium or primary human brain astrocytes within the surrounding collagen gel to explore the ability of this simplified model to identify distinct contributions of these supporting cells to the neuroinflammatory response. This human 3D BBB-on-a-chip exhibited barrier permeability similar to that observed in other in vitro BBB models created with non-human cells, and when stimulated with the inflammatory trigger, tumor necrosis factor-alpha (TNF-α), different secretion profiles for granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) were observed depending on the presence of astrocytes or pericytes. Importantly, the levels of these responses detected in the 3D BBB chip were significantly greater than when the same cells were co-cultured in static Transwell plates. Thus, as G-CSF and IL-6 have been reported to play important roles in neuroprotection and neuroactivation in vivo, this 3D BBB chip potentially offers a new method to study human neurovascular function and inflammation in vitro, and to identify physiological contributions of individual cell types.
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    Robotic fluidic coupling and interrogation of multiple vascularized organ chips
    (Springer Science and Business Media LLC, 2020-01-27) Novak, Richard; Ingram, Miles; Marquez, Susan; Das, Debarun; Delahanty, Aaron; Herland, Anna; Maoz, Ben; Jeanty, Sauveur; Somayaji, Mahadevabharath R.; Burt, Morgan; Calamari, Elizabeth; Chalkiadaki, Angeliki; Cho, Alexander; Choe, Youngjae; Chou, David; Cronce, Michael; Dauth, Stephanie; Divic, Toni; Fernandez-Alcon, Jose; Ferrante, Thomas; Ferrier, John; FitzGerald, Edward; Fleming, Rachel; Jalili Firoozinezhad, Sasan; Grevesse, Thomas; Goss, Josue; Hamkins-Indik, Tiama; Henry, Olivier; Hinojosa, Chris; Huffstater, Tessa; Jang, Kyung-Jin; Kujala, Ville; Leng, Lian; Mannix, Robert; Milton, Yuka; Nawroth, Janna; Nestor, Bret; Ng Pitti, Carlos; O'Connor, Blakely; Park, Tae-Eun; Sanchez, Henry; Sliz, Josiah; Sontheimer-Phelps, Alexandra; Swenor, Ben; Thompson, Guy; Touloumes, George J.; Tranchemontagne, Zachary; Wen, Norman; Yedid, Moran; Bahinski, Anthony; Hamilton, Geraldine; Levner, Daniel; Levy, Oren; Przekwas, Andrzej; Prantil-Baun, Rachelle; Parker, Kevin; Ingber, Donald
    Organ chips can recapitulate organ-level (patho)physiology, yet pharmacokinetic and pharmacodynamic analyses require multi-organ systems linked by vascular perfusion. Here, we describe an ‘Interrogator’ employing liquid-handling robotics, custom software and an integrated mobile microscope for the automated culture, perfusion, medium addition, fluidic linking, sample collection and in situ microscopic imaging of up to 10 Organ Chips inside a standard tissue-culture incubator. The robotic interrogator maintained the viability and organ-specific functions of eight vascularized, two-channel organ chips (intestine, liver, kidney, heart, lung, skin, blood–brain barrier and brain) for 3 weeks in culture when intermittently fluidically coupled via a common blood substitute through their medium reservoirs and endothelium-lined vascular channels. We used the robotic interrogator and a physiological multi-compartmental reduced-order model of the experimental system to quantitatively predict the distribution of an inulin tracer perfused through the multi-organ Human-Body-on-Chips. The automated culture system allows for the imaging of cells in the organ chips, and for repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling.