Three-dimensional Tissue Culture Based on Magnetic Cell Levitation

Overview

Journal Nat Nanotechnol

Specialty Biotechnology

Date 2010 Mar 16

PMID 20228788

Citations 217

Authors

Glauco R Souza

Jennifer R Molina

Robert M Raphael

Michael G Ozawa

Daniel J Stark

Carly S Levin

Lawrence F Bronk

Jeyarama S Ananta

Jami Mandelin

Maria-Magdalena Georgescu

James A Bankson

Juri G Gelovani

T C Killian

Wadih Arap

Renata Pasqualini

Affiliations

Soon will be listed here.

Abstract

Cell culture is an essential tool in drug discovery, tissue engineering and stem cell research. Conventional tissue culture produces two-dimensional cell growth with gene expression, signalling and morphology that can be different from those found in vivo, and this compromises its clinical relevance. Here, we report a three-dimensional tissue culture based on magnetic levitation of cells in the presence of a hydrogel consisting of gold, magnetic iron oxide nanoparticles and filamentous bacteriophage. By spatially controlling the magnetic field, the geometry of the cell mass can be manipulated, and multicellular clustering of different cell types in co-culture can be achieved. Magnetically levitated human glioblastoma cells showed similar protein expression profiles to those observed in human tumour xenografts. Taken together, these results indicate that levitated three-dimensional culture with magnetized phage-based hydrogels more closely recapitulates in vivo protein expression and may be more feasible for long-term multicellular studies.

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References

Abbott A . Cell culture: biology's new dimension. Nature. 2003; 424(6951):870-2. DOI: 10.1038/424870a. View

Cukierman E, Pankov R, Stevens D, Yamada K . Taking cell-matrix adhesions to the third dimension. Science. 2001; 294(5547):1708-12. DOI: 10.1126/science.1064829. View

Langer R, Tirrell D . Designing materials for biology and medicine. Nature. 2004; 428(6982):487-92. DOI: 10.1038/nature02388. View

Meyer C, Alenghat F, Rim P, Fong J, Fabry B, Ingber D . Mechanical control of cyclic AMP signalling and gene transcription through integrins. Nat Cell Biol. 2000; 2(9):666-8. DOI: 10.1038/35023621. View

Souza G, Yonel-Gumruk E, Fan D, Easley J, Rangel R, Guzman-Rojas L . Bottom-up assembly of hydrogels from bacteriophage and Au nanoparticles: the effect of cis- and trans-acting factors. PLoS One. 2008; 3(5):e2242. PMC: 2386289. DOI: 10.1371/journal.pone.0002242. View

Ito A, Shinkai M, Honda H, Kobayashi T . Medical application of functionalized magnetic nanoparticles. J Biosci Bioeng. 2005; 100(1):1-11. DOI: 10.1263/jbb.100.1. View

Ito A, Ino K, Kobayashi T, Honda H . The effect of RGD peptide-conjugated magnetite cationic liposomes on cell growth and cell sheet harvesting. Biomaterials. 2005; 26(31):6185-93. DOI: 10.1016/j.biomaterials.2005.03.039. View

Souza G, Christianson D, Staquicini F, Ozawa M, Snyder E, Sidman R . Networks of gold nanoparticles and bacteriophage as biological sensors and cell-targeting agents. Proc Natl Acad Sci U S A. 2006; 103(5):1215-20. PMC: 1346765. DOI: 10.1073/pnas.0509739103. View

Bhowmick D, Zhuang Z, Wait S, Weil R . A functional polymorphism in the EGF gene is found with increased frequency in glioblastoma multiforme patients and is associated with more aggressive disease. Cancer Res. 2004; 64(4):1220-3. DOI: 10.1158/0008-5472.can-03-3137. View

10.

Wan X, Li Z, Lubkin S . Mechanics of mesenchymal contribution to clefting force in branching morphogenesis. Biomech Model Mechanobiol. 2007; 7(5):417-26. DOI: 10.1007/s10237-007-0105-y. View

11.

Nam K, Kim D, Yoo P, Chiang C, Meethong N, Hammond P . Virus-enabled synthesis and assembly of nanowires for lithium ion battery electrodes. Science. 2006; 312(5775):885-8. DOI: 10.1126/science.1122716. View

12.

Dobson J, Cartmell S, Keramane A, El Haj A . Principles and design of a novel magnetic force mechanical conditioning bioreactor for tissue engineering, stem cell conditioning, and dynamic in vitro screening. IEEE Trans Nanobioscience. 2006; 5(3):173-7. DOI: 10.1109/tnb.2006.880823. View

13.

Chicoine M, Silbergeld D . Mitogens as motogens. J Neurooncol. 1998; 35(3):249-57. DOI: 10.1023/a:1005808315821. View

14.

Griffith L, Swartz M . Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol. 2006; 7(3):211-24. DOI: 10.1038/nrm1858. View

15.

Coleman C, Gonzalez-Villalobos R, Allen P, Johanson K, Guevorkian K, Valles J . Diamagnetic levitation changes growth, cell cycle, and gene expression of Saccharomyces cerevisiae. Biotechnol Bioeng. 2007; 98(4):854-63. DOI: 10.1002/bit.21526. View

16.

Snyder E, Deitcher D, Walsh C, Hartwieg E, Cepko C . Multipotent neural cell lines can engraft and participate in development of mouse cerebellum. Cell. 1992; 68(1):33-51. DOI: 10.1016/0092-8674(92)90204-p. View

17.

Csikasz-Nagy A, Battogtokh D, Chen K, Novak B, Tyson J . Analysis of a generic model of eukaryotic cell-cycle regulation. Biophys J. 2006; 90(12):4361-79. PMC: 1471857. DOI: 10.1529/biophysj.106.081240. View

18.

Petersen O, Ronnov-Jessen L, Howlett A, Bissell M . Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. Proc Natl Acad Sci U S A. 1992; 89(19):9064-8. PMC: 50065. DOI: 10.1073/pnas.89.19.9064. View

19.

Georgescu M, Kirsch K, Akagi T, Shishido T, Hanafusa H . The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region. Proc Natl Acad Sci U S A. 1999; 96(18):10182-7. PMC: 17863. DOI: 10.1073/pnas.96.18.10182. View

20.

Pampaloni F, Reynaud E, Stelzer E . The third dimension bridges the gap between cell culture and live tissue. Nat Rev Mol Cell Biol. 2007; 8(10):839-45. DOI: 10.1038/nrm2236. View