caa a22 4500 605480389 CHVBK 20210128100415.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s10544-014-9918-5 doi (NATIONALLICENCE)springer-10.1007/s10544-014-9918-5 Alginate core-shell beads for simplified three-dimensional tumor spheroid culture and drug screening [Elektronische Daten] [Linfen Yu, Cynthia Ni, Samantha Grist, Carmen Bayly, Karen Cheung] We demonstrate that when using cell-laden core-shell hydrogel beads to support the generation of tumor spheroids, the shell structure reduces the out-of-bead and monolayer cell proliferation that occurs during long-term culture of tumor cells within core-only alginate beads. We fabricate core-shell beads in a two-step process using simple, one-layer microfluidic devices. Tumor cells encapsulated within the bead core will proliferate to form multicellular aggregates which can serve as three-dimensional (3-D) models of tumors in drug screening. Encapsulation in an alginate shell increased the time that cells could be maintained in three-dimensional culture for MCF-7 breast cancer cells prior to out-of-bead proliferation, permitting formation of spheroids over a period of 14 days without the need move the cell-laden beads to clean culture flasks to separate beads from underlying monolayers. Tamoxifen and docetaxel dose response shows decreased toxicity for multicellular aggregates in three-dimensional core-shell bead culture compared to monolayer. Using simple core-only beads gives mixed monolayer and 3-D culture during drug screening, and alters the treatment result compared to the 3-D core-shell or the 2-D monolayer groups, as measured by standard proliferation assay. By preventing the out-of-bead proliferation and subsequent monolayer formation that is observed with core-only beads, the core-shell structure can obviate the requirement to transfer the beads to a new culture flask during drug screening, an important consideration for cell-based drug screening and drugs which have high multicellular resistance index. Springer Science+Business Media New York, 2015 Microfluidics nationallicence 3-D cell culture nationallicence Cell-laden hydrogel beads nationallicence Drug screening nationallicence Yu Linfen Department of Electrical and Computer Engineering, University of British Columbia, 2332 Main Mall, V6T 1Z4, Vancouver, Canada aut Ni Cynthia Department of Electrical and Computer Engineering, University of British Columbia, 2332 Main Mall, V6T 1Z4, Vancouver, Canada aut Grist Samantha Department of Electrical and Computer Engineering, University of British Columbia, 2332 Main Mall, V6T 1Z4, Vancouver, Canada aut Bayly Carmen Department of Electrical and Computer Engineering, University of British Columbia, 2332 Main Mall, V6T 1Z4, Vancouver, Canada aut Cheung Karen Department of Electrical and Computer Engineering, University of British Columbia, 2332 Main Mall, V6T 1Z4, Vancouver, Canada aut Biomedical Microdevices Springer US; http://www.springer-ny.com 17/2(2015-04-01), 1-9 1387-2176 17:2<1 2015 17 10544 https://doi.org/10.1007/s10544-014-9918-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10544-014-9918-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yu Linfen Department of Electrical and Computer Engineering, University of British Columbia, 2332 Main Mall, V6T 1Z4, Vancouver, Canada aut NATIONALLICENCE 700 1- Ni Cynthia Department of Electrical and Computer Engineering, University of British Columbia, 2332 Main Mall, V6T 1Z4, Vancouver, Canada aut NATIONALLICENCE 700 1- Grist Samantha Department of Electrical and Computer Engineering, University of British Columbia, 2332 Main Mall, V6T 1Z4, Vancouver, Canada aut NATIONALLICENCE 700 1- Bayly Carmen Department of Electrical and Computer Engineering, University of British Columbia, 2332 Main Mall, V6T 1Z4, Vancouver, Canada aut NATIONALLICENCE 700 1- Cheung Karen Department of Electrical and Computer Engineering, University of British Columbia, 2332 Main Mall, V6T 1Z4, Vancouver, Canada aut NATIONALLICENCE 773 0- Biomedical Microdevices Springer US; http://www.springer-ny.com 17/2(2015-04-01), 1-9 1387-2176 17:2<1 2015 17 10544