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Ultrasonic three-dimensional on-chip cell culture for dynamic studies of tumor immune surveillance by natural killer cells
KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.ORCID iD: 0000-0002-7023-4772
KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.ORCID iD: 0000-0001-5178-7593
KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
2015 (English)In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 15, no 15, 3222-31 p.Article in journal (Refereed) Published
Abstract [en]

We demonstrate a simple method for three-dimensional (3D) cell culture controlled by ultrasonic standing waves in a multi-well microplate. The method gently arranges cells in a suspension into a single aggregate in each well of the microplate and, by this, nucleates 3D tissue-like cell growth for culture times between two and seven days. The microplate device is compatible with both high-resolution optical microscopy and maintenance in a standard cell incubator. The result is a scaffold- and coating-free method for 3D cell culture that can be used for controlling the cellular architecture, as well as the cellular and molecular composition of the microenvironment in and around the formed cell structures. We demonstrate the parallel production of one hundred synthetic 3D solid tumors comprising up to thousands of human hepatocellular carcinoma (HCC) HepG2 cells, we characterize the tumor structure by high-resolution optical microscopy, and we monitor the functional behavior of natural killer (NK) cells migrating, docking and interacting with the tumor model during culture. Our results show that the method can be used for determining the collective ability of a given number of NK cells to defeat a solid tumor having a certain size, shape and composition. The ultrasound-based method itself is generic and can meet any demand from applications where it is advantageous to monitor cell culture from production to analysis of 3D tissue or tumor models using microscopy in one single microplate device.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2015. Vol. 15, no 15, 3222-31 p.
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:kth:diva-171262DOI: 10.1039/c5lc00436eISI: 000358022900015PubMedID: 26126574Scopus ID: 2-s2.0-84948403565OAI: oai:DiVA.org:kth-171262DiVA: diva2:843313
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research
Note

QC 20150728

Available from: 2015-07-28 Created: 2015-07-27 Last updated: 2017-12-04Bibliographically approved

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Ohlin, MathiasÖnfelt, Björn

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