Abstract:
:Current animal and 2-D cell culture models employed in metastasis research and drug discovery remain poor mimics of human cancer physiology. Here we describe a "metastasis-on-a-chip" system allowing real time tracking of fluorescent colon cancer cells migrating from hydrogel-fabricated gut constructs to downstream liver constructs within a circulatory fluidic device system that responds to environmental manipulation and drug treatment. Devices consist of two chambers in which gut and liver constructs are housed independently, but are connected in series via circulating fluid flow. Constructs were biofabricated with a hyaluronic acid-based hydrogel system, capable of a variety of customizations, inside of which representative host tissue cells were suspended and metastatic colon carcinoma tumor foci were created. The host tissue of the constructs expressed normal epithelial markers, which the tumor foci failed to express. Instead, tumor regions lost membrane-bound adhesion markers, and expressed mesenchymal and proliferative markers, suggesting a metastatic phenotype. Metastatic tumor foci grew in size, eventually disseminating from the intestine construct and entering circulation, subsequently reaching in the liver construct, thus mimicking some of the migratory events observed during metastasis. Lastly, we demonstrated the ability to manipulate the system, including chemically modulating the hydrogel system mechanical properties and administering chemotherapeutic agents, and evaluated the effects of these parameters on invasive tumor migration. These results describe the capability of this early stage metastasis-on-a-chip system to model several important characteristics of human metastasis, thereby demonstrating the potential of the platform for making meaningful advances in cancer investigation and drug discovery. Biotechnol. Bioeng. 2016;113: 2020-2032. © 2016 Wiley Periodicals, Inc.
journal_name
Biotechnol Bioengjournal_title
Biotechnology and bioengineeringauthors
Skardal A,Devarasetty M,Forsythe S,Atala A,Soker Sdoi
10.1002/bit.25950subject
Has Abstractpub_date
2016-09-01 00:00:00pages
2020-32issue
9eissn
0006-3592issn
1097-0290journal_volume
113pub_type
杂志文章abstract::Mammalian cell lines for recombinant protein production need to maintain productivity over extended cultivation times. Long-term stability studies are time and resource intensive, but are widely performed to identify and eliminate unstable candidates during cell line development. Production instability of manufacturin...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.23216
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abstract::A limited life cycle assessment (LCA) was performed on a combined biological and chemical process for the production of adipic acid, which was compared to the traditional petrochemical process. The LCA comprises the biological conversion of the aromatic feedstocks benzoic acid, impure aromatics, toluene, or phenol fro...
journal_title:Biotechnology and bioengineering
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doi:10.1002/bit.23074
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abstract::Previous studies suggest that secretion of cloned proteins synthesized by recombinant Chinese hamster ovary (CHO) cells can be adenosine triphosphate (ATP) limited. Other research indicates that the presence of cloned Vitreoscilla hemoglobin (VHb) enhances ATP production in oxygen-limited Escherichia coli. To evaluate...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260441114
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abstract::In this work the question was addressed if in nitrite-oxidizing activated sludge systems the environmental competition between Nitrobacter spp. and Nitrospira spp., which only recently has been discovered to play a role in these systems, is affected by the nitrite concentrations. Two parallel chemostats were inoculate...
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pub_type: 杂志文章
doi:10.1002/bit.21004
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abstract::Cultures with immobilized hybridoma cells were performed in fixed bed systems. "Steady state" values for volume-specific substrate uptake and metabolite production rates were determined at various perfusion rates and superficial flow velocities of the medium within the carrier matrix. Data from fixed bed volumes betwe...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0290(19970805)55:3<535::AID-BIT
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abstract::The denitrification capability of Cluster 1 Defluviicoccus vanus-related glycogen-accumulating organisms (DvGAOs) is investigated. A sequencing batch reactor (SBR) fed with acetate as the sole carbon source was operated under alternating anaerobic-aerobic conditions to enrich Cluster 1 DvGAOs. Fluorescence in situ hyb...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.21711
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abstract::Recently it has been established that low molecular weight displacers can be successfully employed for the purification of proteins in hydrophobic interaction chromatography (HIC) systems. This work investigates the utility of this technique for the purification of an industrial protein mixture. The study involved the...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.10582
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abstract::Metabolic carbon labelling experiments enable a large amount of extracellular fluxes and intracellular carbon isotope enrichments to be measured. Since the relation between the measured quantities and the unknown intracellular metabolic fluxes is given by bilinear balance equations, flux determination from this data s...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0290(19970705)55:1<118::AID-BIT
更新日期:1997-07-05 00:00:00
abstract::Dilute aqueous solutions of polymers released by marine phytoplankton (microalgae) were shown to effectively reduce drag in capillary pipe flow. Tests were performed in a capillary turbulent flow viscometer which extruded small samples under high pressures. In all, 22 species were screened, and the products of one chl...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260330506
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journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.20225
更新日期:2004-10-20 00:00:00
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journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260340603
更新日期:1989-09-01 00:00:00
abstract::Lignin, one of the major components of lignocellulosic biomass, plays an inhibitory role on the enzymatic hydrolysis of cellulose. This work examines the role of lignin in pretreated hardwood, where extents of cellulose hydrolysis decrease, rather than increase with increasing severity of liquid hot water pretreatment...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章,评审
doi:10.1002/bit.25349
更新日期:2015-02-01 00:00:00
abstract::The insect larvae/baculovirus protein production process was dramatically simplified by expressing fusion proteins containing green fluorescent protein (GFP) and the product-of-interest. In this case, human interleukin-2 (hIL-2) and chloramphenicol acetyl-transferase (CAT) were model products. Specifically, our fusion...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/(sici)1097-0290(19991105)65:3<316::aid-bit
更新日期:1999-11-05 00:00:00
abstract::The evolution of microbial populations involved in simulated-heap leaching of a polymetallic black schist sulfide ore (from the recently-commissioned Talvivaara mine, Finland) was monitored in aerated packed bed column reactors over a period of 40 weeks. The influence of ore particle size (2-6.5 mm and 6.5-12 mm) on c...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.21951
更新日期:2008-11-01 00:00:00
abstract::The key objective for recombinant protein production in bacteria is the maximum exploitation of the cell factory's potential, whereby often strong expression vectors are used to increase product yield. If the metabolic load caused by recombinant expression exceeds the host's capacity, the system exhausts itself, resul...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.10104
更新日期:2002-01-20 00:00:00
abstract::The feasibility of continuous production of proteins in chemostat cultures of Bacillus subtilis was investigated. An expression system consisting of the bacterium B. subtilis BR151 carrying plasmid p602/19 was used. The plasmid contains the cat (chioramphenicol acetyltrans-ferase) gene downstream of a strong vegetativ...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260470503
更新日期:1995-09-05 00:00:00
abstract::Thermodynamic feasibility analysis (TFA) has been used as a tool capable of providing additional constraints to the mass balance-based methods of analysis of metabolic networks (e.g., flux balance analysis). Several publications have recently appeared in which TFA of different metabolic pathways from relatively simple...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.22309
更新日期:2009-07-01 00:00:00
abstract::Compared to the conventional microbial and mammalian systems, transgenic plants produce proteins in a different matrix. This provides opportunities and challenges for downstream processing. In the context of the plant host Brassica napus (canola), this work addresses the bioprocessing challenges of solid fractionation...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.10524
更新日期:2003-03-30 00:00:00
abstract::Chinese hamster ovary (CHO) cells in culture are known to consume large amounts of nutrients and divert most of them toward byproducts, some of which, including lactate and ammonia, are known to be toxic in nature. Glucose limitation strategies can successfully control lactate accumulation in fed-batch cultures yieldi...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.26313
更新日期:2017-08-01 00:00:00
abstract::Addition of Tween 85 to aqueous suspensions of Anabaena variabilis induced photosynthetic evolution of hydrogen over a time span of several weeks: As much as 148 nmol H(2)/h . mg dry weight was produced in the first week by a suspension containing 4.2 mg dry weight of cells and 77 mM Tween 85. The chemical structure o...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260420812
更新日期:1993-10-01 00:00:00
abstract::Pancreatic islet transplantation is a promising alternative to whole-pancreas transplantation as a treatment of type 1 diabetes mellitus. This technique has been extensively developed during the past few years, with the main purpose of minimizing the complications arising from the standard protocols used in organ tran...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章,评审
doi:10.1002/bit.26821
更新日期:2018-12-01 00:00:00
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journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.25188
更新日期:2014-06-01 00:00:00
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journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260240106
更新日期:1982-01-01 00:00:00
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journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.23130
更新日期:2011-08-01 00:00:00
abstract::To investigate the effects of factors secreted by different cell lines on human monoclonal antibody (MAb) integrity, 600 mg of a human MAb, which specifically binds to human erythrocytes, were produced in a perfusion process. After purification by protein A affinity chromatography, the MAb was used for integrity testi...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260450202
更新日期:1995-01-20 00:00:00
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journal_title:Biotechnology and bioengineering
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doi:10.1002/bit.22842
更新日期:2010-11-01 00:00:00
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journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.27503
更新日期:2020-07-15 00:00:00
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journal_title:Biotechnology and bioengineering
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doi:10.1002/bit.20955
更新日期:2006-09-05 00:00:00
abstract::Biopharmaceutical production would benefit from rapid methods to optimize production of therapeutic proteins by screening host cell line/vector combination, culture media, and operational parameters such as timing of induction. Miniaturized bioreactors are an emerging research area aiming at improving the development ...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.21751
更新日期:2008-05-01 00:00:00
abstract::We developed a method for the fast sorting and selection of mammalian cells expressing and secreting a protein at high levels. This procedure relies on cell capture using an automated microfluidic device handling antibody-coupled magnetic microparticles and on a timed release of the cells from the microparticles after...
journal_title:Biotechnology and bioengineering
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