title: Alginate core-shell beads for simplified three-dimensional tumor spheroid culture and drug screening.
abstract: 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.
authors: Department of Electrical and Computer Engineering, University of British Columbia, 2332 Main Mall, Vancouver, V6T 1Z4, Canada.
authors: Linfen
authors: L
authors: Yu
authors: Cynthia
authors: C
authors: Ni
authors: Samantha M
authors: SM
authors: Grist
authors: Carmen
authors: C
authors: Bayly
authors: Karen C
authors: KC
authors: Cheung
mesh_terms: D000464:Alginates / Q000737:chemistry*; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D049109:Cell Proliferation; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020100:Hydrogels; D056656:Lab-On-A-Chip Devices; D061986:MCF-7 Cells / Q000187:drug effects; D008863:Microspheres; D013629:Tamoxifen / Q000494:pharmacology; D043823:Taxoids / Q000494:pharmacology
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020100:Hydrogels; D043823:Taxoids; D013629:Tamoxifen; D000077143:Docetaxel; D020723:Glucuronic Acid