Skip to main content
Top
Published in:

Open Access 01-12-2017 | Short report

Microfluidic device for primary tumor spheroid isolation

Authors: Jiaojiao Zhou, Jimmy Su, Xiaotong Fu, Lei Zheng, Zhizhong Yin

Published in: Experimental Hematology & Oncology | Issue 1/2017

Login to get access

Abstract

Background

Traditional two-dimensional (2-D) monolayer cell culture is vastly different from in vivo physiological conditions, which can lead to inaccurate or insufficient data in areas where response and efficacy within humans are being investigated, such as drug discovery, pathology studies, etc. Misleading results arise from two main disadvantages of monolayer cell culture. First, after several passages, cell lines lose many features from their original in vivo state. Second, the morphology of cells cultured in a monolayer is much different from the cell morphology in three-dimensional (3-D) in vivo conditions, thus resulting in altered cellular function. Three-dimensional multi-cellular spheroids, on the other hand, are a better representation of in vivo physiological conditions while still retaining many of the in vitro cell culture advantages. Primary spheroids freshly isolated from tissue samples are especially ideal for cell-based assays by avoiding the two problems of 2-D monolayer cell culture.

Methods

In this paper, we report a microfluidic device for primary tumor spheroid isolation. Pancreatic tumor samples from mice were used in the experiments.

Results

We successfully isolated primary tumor spheroids from the pancreatic tumor samples and were able to maintain the spheroids in culture for up to two weeks.

Conclusions

This novel microfluidic device may promote and advance the isolation of primary tumor spheroids for future drug testing and interrogation of tumor characteristics.
Literature
2.
go back to reference Breslin S, O’Driscoll L. Three-dimensional cell culture: the missing link in drug discovery. Drug Discov Today. 2013;18:240–9.CrossRefPubMed Breslin S, O’Driscoll L. Three-dimensional cell culture: the missing link in drug discovery. Drug Discov Today. 2013;18:240–9.CrossRefPubMed
3.
go back to reference DiMasi JA, Grabowski HG. Economics of new oncology drug development. J Clin Oncol. 2007;25:209–16.CrossRefPubMed DiMasi JA, Grabowski HG. Economics of new oncology drug development. J Clin Oncol. 2007;25:209–16.CrossRefPubMed
4.
go back to reference Edmondson R, et al. Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay Drug Dev Technol. 2014;12:207–18.CrossRefPubMedPubMedCentral Edmondson R, et al. Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay Drug Dev Technol. 2014;12:207–18.CrossRefPubMedPubMedCentral
5.
go back to reference Ingber DE. Reverse engineering human pathophysiology with organs-on-chips. Cell. 2016;164(6):1105–9.CrossRefPubMed Ingber DE. Reverse engineering human pathophysiology with organs-on-chips. Cell. 2016;164(6):1105–9.CrossRefPubMed
6.
go back to reference Kelm JM, et al. Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types. Biotechnol Bioeng. 2003;83(2):173–80.CrossRefPubMed Kelm JM, et al. Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types. Biotechnol Bioeng. 2003;83(2):173–80.CrossRefPubMed
7.
go back to reference Alessandri K, et al. Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro. PNAS. 2013;110:14843–8.CrossRefPubMedPubMedCentral Alessandri K, et al. Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro. PNAS. 2013;110:14843–8.CrossRefPubMedPubMedCentral
8.
9.
go back to reference Chen Y-C, et al. High-throughput cancer cell sphere formation for characterizing the efficacy of photo dynamic therapy in 3D cell cultures. Sci Rep. 2015;5:12175.CrossRefPubMedPubMedCentral Chen Y-C, et al. High-throughput cancer cell sphere formation for characterizing the efficacy of photo dynamic therapy in 3D cell cultures. Sci Rep. 2015;5:12175.CrossRefPubMedPubMedCentral
10.
go back to reference Patra B, et al. A microfluidic device for uniform-sized cell spheroids formation, culture, harvesting and flow cytometry analysis. Biomicrofluidics. 2013;7:054114.CrossRefPubMedCentral Patra B, et al. A microfluidic device for uniform-sized cell spheroids formation, culture, harvesting and flow cytometry analysis. Biomicrofluidics. 2013;7:054114.CrossRefPubMedCentral
11.
go back to reference Wu LY, Carlo DD, Lee LP. Microfluidic self-assembly of tumor spheroids for anticancer drug discovery. Biomed Microdevices. 2008;10:197–202.CrossRefPubMed Wu LY, Carlo DD, Lee LP. Microfluidic self-assembly of tumor spheroids for anticancer drug discovery. Biomed Microdevices. 2008;10:197–202.CrossRefPubMed
13.
go back to reference Boj SF, et al. Organoid models of human and mouse ductal pancreatic cancer. Cell. 2015;160:324–38.CrossRefPubMed Boj SF, et al. Organoid models of human and mouse ductal pancreatic cancer. Cell. 2015;160:324–38.CrossRefPubMed
16.
go back to reference Mehtaa G, et al. Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy. J Control Release. 2012;164(2):192–204.CrossRef Mehtaa G, et al. Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy. J Control Release. 2012;164(2):192–204.CrossRef
17.
go back to reference Maqsood MI, et al. Immortality of cell lines: challenges and advantages of establishment. Cell Biol Int. 2013;37:1038–45.CrossRefPubMed Maqsood MI, et al. Immortality of cell lines: challenges and advantages of establishment. Cell Biol Int. 2013;37:1038–45.CrossRefPubMed
18.
go back to reference Hewitt NJ, Lechón MJG. Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies. Drug Metab Rev. 2007;39:159–234.CrossRefPubMed Hewitt NJ, Lechón MJG. Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies. Drug Metab Rev. 2007;39:159–234.CrossRefPubMed
19.
go back to reference Stadler M, et al. Increased complexity in carcinomas: analyzing and modeling the interaction of human cancer cells with their microenvironment. Cancer Biol. 2015;35:107–24.CrossRef Stadler M, et al. Increased complexity in carcinomas: analyzing and modeling the interaction of human cancer cells with their microenvironment. Cancer Biol. 2015;35:107–24.CrossRef
21.
go back to reference Yin Z, et al. An integrated micro-electro-fluidic and protein arraying system for parallel analysis of cell responses to controlled microenvironments. Integr Biol. 2010;2:416–23.CrossRef Yin Z, et al. An integrated micro-electro-fluidic and protein arraying system for parallel analysis of cell responses to controlled microenvironments. Integr Biol. 2010;2:416–23.CrossRef
22.
go back to reference Luongo K, et al. Microfluidic device for trapping and monitoring three dimensional multicell spheroids using electrical impedance spectroscopy. Biomicrofluidics. 2013;7:034108.CrossRefPubMedCentral Luongo K, et al. Microfluidic device for trapping and monitoring three dimensional multicell spheroids using electrical impedance spectroscopy. Biomicrofluidics. 2013;7:034108.CrossRefPubMedCentral
23.
go back to reference Weizman N, Krelin Y, Shabtay-Orbach A, et al. Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase. Oncogene. 2014;33(29):3812.CrossRefPubMed Weizman N, Krelin Y, Shabtay-Orbach A, et al. Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase. Oncogene. 2014;33(29):3812.CrossRefPubMed
24.
go back to reference Lee J, Yakubov B, Ivan C, et al. Tissue transglutaminase activates cancer-associated fibroblasts and contributes to gemcitabine resistance in pancreatic cancer. Neoplasia. 2016;18(11):689–98.CrossRefPubMedPubMedCentral Lee J, Yakubov B, Ivan C, et al. Tissue transglutaminase activates cancer-associated fibroblasts and contributes to gemcitabine resistance in pancreatic cancer. Neoplasia. 2016;18(11):689–98.CrossRefPubMedPubMedCentral
Metadata
Title
Microfluidic device for primary tumor spheroid isolation
Authors
Jiaojiao Zhou
Jimmy Su
Xiaotong Fu
Lei Zheng
Zhizhong Yin
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Experimental Hematology & Oncology / Issue 1/2017
Electronic ISSN: 2162-3619
DOI
https://doi.org/10.1186/s40164-017-0084-3

ASH 2024 Annual Meeting Coverage

inMIND supports tafasitamab addition in follicular lymphoma

Combining tafasitamab with lenalidomide and rituximab significantly improves progression-free survival for patients with relapsed or refractory follicular lymphoma.

Featuring the official presentation video

Read more
SPONSORED

Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

In this webinar, Professor Martin Dreyling and an esteemed international panel of CAR T-cell therapy experts discuss the latest data on the safety, efficacy, and clinical impact of CAR T-cell therapies in the treatment of r/r DLBCL and r/r FL.

Please note, this webinar is not intended for healthcare professionals based in the US and UK.

Sponsored by:
  • Novartis Pharma AG
Chaired by: Prof. Martin Dreyling
Developed by: Springer Healthcare
Watch now