A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications

التفاصيل البيبلوغرافية
العنوان: A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications
المؤلفون: Xiaolin Wang, Da Zhao, Abraham P. Lee, Agua Sobrino, Brianna M. Craver, Lilian Y. N. Lee, Duc T. T. Phan, Jerry C. Chen, Christopher C.W. Hughes, Steven C. George
المصدر: Lab on a Chip. 17:511-520
بيانات النشر: Royal Society of Chemistry (RSC), 2017.
سنة النشر: 2017
مصطلحات موضوعية: 0301 basic medicine, Drug, Computer science, media_common.quotation_subject, Hydrostatic pressure, Cell Culture Techniques, Drug Evaluation, Preclinical, Biomedical Engineering, Antineoplastic Agents, Bioengineering, 02 engineering and technology, Biochemistry, Organ-on-a-chip, Article, 03 medical and health sciences, In vivo, Humans, media_common, Neovascularization, Pathologic, Low toxicity, Drug screens, Extramural, Gene Expression Profiling, Equipment Design, Neoplasms, Experimental, General Chemistry, Microfluidic Analytical Techniques, 021001 nanoscience & nanotechnology, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Tissue Array Analysis, 0210 nano-technology, Biomedical engineering
الوصف: There is a growing awareness that complex 3-dimensional (3D) organs are not well represented by monolayers of a single cell type – the standard format for many drug screens. To address this deficiency, and with the goal of improving screens so that drugs with good efficacy and low toxicity can be identified, microphysiological systems (MPS) are being developed that better capture the complexity of in vivo physiology. We have previously described an organ-on-a-chip platform that incorporates perfused microvessels, such that survival of the surrounding tissue is entirely dependent on delivery of nutrients through the vessels. Here we describe an arrayed version of the platform that incorporates multiple Vascularized Micro-Organs (VMOs) on a 96-well plate. Each VMO is independently-addressable and flow through the micro-organ is driven by hydrostatic pressure. The platform is easy to use, requires no external pumps or valves, and is highly reproducible. As a proof-of-concept we have created arrayed Vascularized Micro Tumors (VMTs) and used these in a blinded screen to assay a small library of compounds, including FDA-approved anti-cancer drugs, and successfully identified both anti-angiogenic and anti-tumor drugs. This 3D platform is suitable for efficacy/toxicity screening against multiple tissues in a more physiological environment than previously possible.
تدمد: 1473-0189
1473-0197
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc0550067a97d166c011ae7c71381653
https://doi.org/10.1039/c6lc01422d
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....fc0550067a97d166c011ae7c71381653
قاعدة البيانات: OpenAIRE