Alginate core-shell beads for simplified three-dimensional tumor spheroid culture and drug screening

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• 作者：Linfen Yu (1)
  Cynthia Ni (1)
  Samantha M. Grist (1)
  Carmen Bayly (1)
  Karen C. Cheung (1)
  
  1. Department of Electrical and Computer Engineering ; University of British Columbia ; 2332 Main Mall ; Vancouver ; V6T 1Z4 ; Canada
  
• 关键词：Microfluidics ; 3 ; D cell culture ; Cell ; laden hydrogel beads ; Drug screening
• 刊名：Biomedical Microdevices
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：17
• 期：2
• 全文大小：3,458 KB
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• 刊物类别：Engineering
• 刊物主题：Biomedical Engineering
  Biophysics and Biomedical Physics
  Nanotechnology
  Engineering Fluid Dynamics
  
• 出版者：Springer Netherlands
• ISSN：1572-8781

文摘

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.