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Christoffersson, JonasORCID iD iconorcid.org/0000-0001-5914-2837
Publications (7 of 7) Show all publications
Christoffersson, J., Aronsson, C., Jury, M., Selegård, R., Aili, D. & Mandenius, C.-F. (2019). Fabrication of modular hyaluronan-PEG hydrogels to support 3D cultures of hepatocytes in a perfused liver-on-a-chip device. Biofabrication, 11(1), Article ID 015013.
Open this publication in new window or tab >>Fabrication of modular hyaluronan-PEG hydrogels to support 3D cultures of hepatocytes in a perfused liver-on-a-chip device
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2019 (English)In: Biofabrication, ISSN 1758-5082, E-ISSN 1758-5090, Vol. 11, no 1, article id 015013Article in journal (Refereed) Published
Abstract [en]

Liver cell culture models are attractive in both tissue engineering and for development of assays for drug toxicology research. To retain liver specific cell functions, the use of adequate cell types and culture conditions, such as a 3Dorientation of the cells and a proper supply of nutrients and oxygen, are critical. In this article, we show how extracellular matrix mimetic hydrogels can support hepatocyte viability and functionality in a perfused liver-on-a-chip device. A modular hydrogel system based on hyaluronan and poly(ethylene glycol) (HA-PEG), modified with cyclooctyne moieties for bioorthogonal strain-promoted alkyne-azide 1, 3-dipolar cycloaddition (SPAAC), was developed, characterized, and compared for cell compatibility to hydrogels based on agarose and alginate. Hepatoma cells (HepG2) formed spheroids with viable cells in all hydrogels with the highest expression of albumin and urea in alginate hydrogels. By including an excess of cyclooctyne in theHA backbone, azide-modified cell adhesion motifs (linear and cyclicRGDpeptides) could be introduced in order to enhance viability and functionality of human induced pluripotent stem cell derived hepatocytes (hiPS-HEPs). In the HA-PEG hydrogels modified with cyclicRGDpeptides hiPS-HEPs migrated and grew in 3D and showed an increased viability and higher albumin production compared to when cultured in the other hydrogels. This flexible SPAAC crosslinked hydrogel system enabled fabrication of perfused 3D cell culture of hiPS-HEPs and is a promising material for further development and optimization of liver-on-a-chip devices.

Place, publisher, year, edition, pages
Institute of Physics Publishing (IOPP), 2019
Keywords
Organ-on-a-chip; biofabrication; bioorthogonal crosslinking; cell-binding motif; microfluidics
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-153971 (URN)10.1088/1758-5090/aaf657 (DOI)000454550900002 ()30523863 (PubMedID)2-s2.0-85059228017 (Scopus ID)
Note

Funding Agencies|EU Innovative Medicines Initiative Joint Undertaking [115439]; European Union; Swedish Research Council (VR) [B0431901]; Swedish Foundation for Strategic Research (SFF) [FFL15-0026]; Carl Trygger Foundation [CTS15:79]; Knut and Alice Wallenberg Foundation [KAW 2016.0231]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009-00971]

Available from: 2019-01-22 Created: 2019-01-22 Last updated: 2019-02-01Bibliographically approved
Christoffersson, J., Meier, F., Kempf, H., Schwanke, K., Coffee, M., Beilmann, M., . . . Mandenius, C.-F. (2018). A Cardiac Cell Outgrowth Assay for Evaluating Drug Compounds Using a Cardiac Spheroid-on-a-Chip Device. Bioengineering, 5(2), 1-13, Article ID 36.
Open this publication in new window or tab >>A Cardiac Cell Outgrowth Assay for Evaluating Drug Compounds Using a Cardiac Spheroid-on-a-Chip Device
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2018 (English)In: Bioengineering, E-ISSN 2306-5354, Vol. 5, no 2, p. 1-13, article id 36Article in journal (Refereed) Published
Abstract [en]

Three-dimensional (3D) models with cells arranged in clusters or spheroids have emerged as valuable tools to improve physiological relevance in drug screening. One of the challenges with cells cultured in 3D, especially for high-throughput applications, is to quickly and non-invasively assess the cellular state in vitro. In this article, we show that the number of cells growing out from human induced pluripotent stem cell (hiPSC)-derived cardiac spheroids can be quantified to serve as an indicator of a drug’s effect on spheroids captured in a microfluidic device. Combining this spheroid-on-a-chip with confocal high content imaging reveals easily accessible, quantitative outgrowth data. We found that effects on outgrowing cell numbers correlate to the concentrations of relevant pharmacological compounds and could thus serve as a practical readout to monitor drug effects. Here, we demonstrate the potential of this semi-high-throughput “cardiac cell outgrowth assay” with six compounds at three concentrations applied to spheroids for 48 h. The image-based readout complements end-point assays or may be used as a non-invasive assay for quality control during long-term culture.

National Category
Cell and Molecular Biology Biomedical Laboratory Science/Technology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:liu:diva-154007 (URN)10.3390/bioengineering5020036 (DOI)
Available from: 2019-01-22 Created: 2019-01-22 Last updated: 2019-03-29Bibliographically approved
Bengtsson, K., Christoffersson, J., Mandenius, C.-F. & Robinson, N. D. (2018). A clip-on electroosmotic pump for oscillating flow in microfluidic cell culture devices. Microfluidics and Nanofluidics, 22(3), Article ID 27.
Open this publication in new window or tab >>A clip-on electroosmotic pump for oscillating flow in microfluidic cell culture devices
2018 (English)In: Microfluidics and Nanofluidics, ISSN 1613-4982, E-ISSN 1613-4990, Vol. 22, no 3, article id 27Article in journal (Refereed) Published
Abstract [en]

Recent advances in microfluidic devices put a high demand on small, robust and reliable pumps suitable for high-throughput applications. Here we demonstrate a compact, low-cost, directly attachable (clip-on) electroosmotic pump that couples with standard Luer connectors on a microfluidic device. The pump is easy to make and consists of a porous polycarbonate membrane and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) electrodes. The soft electrode and membrane materials make it possible to incorporate the pump into a standard syringe filter holder, which in turn can be attached to commercial chips. The pump is less than half the size of the microscope slide used for many commercial lab-on-a-chip devices, meaning that these pumps can be used to control fluid flow in individual reactors in highly parallelized chemistry and biology experiments. Flow rates at various electric current and device dimensions are reported. We demonstrate the feasibility and safety of the pump for biological experiments by exposing endothelial cells to oscillating shear stress (up to 5 dyn/cm2) and by controlling the movement of both micro- and macroparticles, generating steady or oscillatory flow rates up to ± 400 μL/min.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2018
National Category
Other Medical Biotechnology
Identifiers
urn:nbn:se:liu:diva-145301 (URN)10.1007/s10404-018-2046-4 (DOI)000427527600005 ()
Note

Funding agencies: Swedish Research Council (Vetenskapsradet) [2015-03298]

Available from: 2018-02-21 Created: 2018-02-21 Last updated: 2019-01-22Bibliographically approved
Christoffersson, J., Aronsson, C., Jury, M., Selegård, R., Aili, D. & Mandenius, C.-F. (2018). Fabrication of modular hyaluronan-PEG hydrogels to support 3D cultures of hepatocytes in a perfused liver-on-a-chip device. Biofabrication, 11(1), 1-13, Article ID 015013.
Open this publication in new window or tab >>Fabrication of modular hyaluronan-PEG hydrogels to support 3D cultures of hepatocytes in a perfused liver-on-a-chip device
Show others...
2018 (English)In: Biofabrication, ISSN 1758-5082, E-ISSN 1758-5090, Vol. 11, no 1, p. 1-13, article id 015013Article in journal (Refereed) Published
Abstract [en]

Liver cell culture models are attractive in both tissue engineering and for development of assays for drug toxicology research. To retain liver specific cell functions, the use of adequate cell types and culture conditions, such as a 3D orientation of the cells and a proper supply of nutrients and oxygen, are critical. In this article, we show how extracellular matrix mimetic hydrogels can support hepatocyte viability and functionality in a perfused liver-on-a-chip device. A modular hydrogel system based on hyaluronan and poly(ethylene glycol) (HA-PEG), modified with cyclooctyne moieties for bioorthogonal strain-promoted alkyne-azide 1, 3-dipolar cycloaddition (SPAAC), was developed, characterized, and compared for cell compatibility to hydrogels based on agarose and alginate. Hepatoma cells (HepG2) formed spheroids with viable cells in all hydrogels with the highest expression of albumin and urea in alginate hydrogels. By including an excess of cyclooctyne in the HA backbone, azide-modified cell adhesion motifs (linear and cyclic RGD peptides) could be introduced in order to enhance viability and functionality of human induced pluripotent stem cell derived hepatocytes (hiPS-HEPs). In the HA-PEG hydrogels modified with cyclic RGD peptides hiPS-HEPs migrated and grew in 3D and showed an increased viability and higher albumin production compared to when cultured in the other hydrogels. This flexible SPAAC crosslinked hydrogel system enabled fabrication of perfused 3D cell culture of hiPS-HEPs and is a promising material for further development and optimization of liver-on-a-chip devices.

Place, publisher, year, edition, pages
Institute of Physics (IOP), 2018
National Category
Cell and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell Biology
Identifiers
urn:nbn:se:liu:diva-154008 (URN)10.1088/1758-5090/aaf657 (DOI)
Available from: 2019-01-22 Created: 2019-01-22 Last updated: 2019-01-22Bibliographically approved
Christoffersson, J. (2018). Organs-on-chips for the pharmaceutical development process: design perspectives and implementations. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Organs-on-chips for the pharmaceutical development process: design perspectives and implementations
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Organs-on-chips are dynamic cell culture devices created with the intention to mimic organ function in vitro. Their purpose is to assess the toxicity and efficacy of drugs and, as early as possible in the pharmaceutical development process, predict the outcome of clinical trials. The aim of this thesis is to explain and discuss these cell culture devices from a design perspective and to experimentally exemplify some of the specific functions that characterize organs-on-chips.

The cells in our body reside in complex environments with chemical and mechanical cues that affect their function and purpose. Such a complex environment is difficult to recreate in the laboratory and has therefore been overlooked in favor of more simple models, i.e. static twodimensional (2D) cell cultures. Numerous recent reports have shown cell culture systems that can resemble the cell’s natural habitat and enhance cell functionality and thereby potentially provide results that better reflects animal and human trials. The way these organs-on-chips improve in vitro cell culture assays is to include e.g. a three-dimensional cell architecture (3D), mechanical stimuli, gradients of oxygen or nutrients, or by combining several relevant cell types that affect each other in close proximity.

The research conducted for this thesis shows how cells in 3D spheroids or in 3D hydrogels can be cultured in perfused microbioreactors. Furthermore, a pump based on electroosmosis, and a method for an objective conceptual design process, is introduced to the field of organs-on-chips.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2018. p. 78
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1907
Keywords
Organs-on-chips, cell culture models, pharmaceutical development, microfluidics
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-145300 (URN)10.3384/diss.diva-145300 (DOI)9789176853597 (ISBN)
Public defence
2018-03-23, Planck, Fysikhuset, Campus Valla, Linköping, 13:30 (English)
Opponent
Supervisors
Note

I den tryckta versionen är det ena serienamnet felaktigt. I den elektroniska versionen är detta ändrat till korrekt "Linköping Studies in Science and Technology. Dissertations"

Available from: 2018-02-21 Created: 2018-02-21 Last updated: 2019-09-26Bibliographically approved
Bergström, G., Christoffersson, J., Schwanke, K., Zweigerdt, R. & Mandenius, C.-F. (2015). Stem cell derived in vivo-like human cardiac bodies in a microfluidic device for toxicity testing by beating frequency imaging. Lab on a Chip, 15(15), 3242-3249
Open this publication in new window or tab >>Stem cell derived in vivo-like human cardiac bodies in a microfluidic device for toxicity testing by beating frequency imaging
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2015 (English)In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 15, no 15, p. 3242-3249Article in journal (Refereed) Published
Abstract [en]

Beating in vivo-like human cardiac bodies (CBs) were used in a microfluidic device for testing cardiotoxicity. The CBs, cardiomyocyte cell clusters derived from induced pluripotent stem cells, exhibited typical structural and functional properties of the native human myocardium. The CBs were captured in niches along a perfusion channel in the device. Video imaging was utilized for automatic monitoring of the beating frequency of each individual CB. The device allowed assessment of cardiotoxic effects on the 3D clustered cardiomyocytes from the drug substances doxorubicin, verapamil and quinidine. Beating frequency data recorded over a period of 6 hours are presented and compared to literature data. The results indicate that this microfluidic setup with imaging of CB characteristics provides a new opportunity for label-free, non-invasive investigation of toxic effects in a 3D microenvironment.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2015
National Category
Biological Sciences Physical Sciences
Identifiers
urn:nbn:se:liu:diva-118294 (URN)10.1039/c5lc00449g (DOI)000358022900017 ()
Available from: 2015-05-26 Created: 2015-05-26 Last updated: 2019-01-22Bibliographically approved
Ghavami, S., Shojaei, S., Yeganeh, B., Ande, S. R., Jangamreddy, J. R., Mehrpour, M., . . . Łos, M. J. (2014). Autophagy and Apoptosis Dysfunction in Neurodegenerative Disorders. Progress in Neurobiology, 112, 24-49
Open this publication in new window or tab >>Autophagy and Apoptosis Dysfunction in Neurodegenerative Disorders
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2014 (English)In: Progress in Neurobiology, ISSN 0301-0082, E-ISSN 1873-5118, Vol. 112, p. 24-49Article, review/survey (Refereed) Published
Abstract [en]

Autophagy and apoptosis are basic physiologic processes contributing to the maintenance of cellular homeostasis. Autophagy encompasses pathways that target long-lived cytosolic proteins and damaged organelles. It involves a sequential set of events including double membrane formation, elongation, vesicle maturation and finally delivery of the targeted materials to the lysosome. Apoptotic cell death is best described through its morphology. It is characterized by cell rounding, membrane blebbing, cytoskeletal collapse, cytoplasmic condensation, and fragmentation, nuclear pyknosis, chromatin condensation/fragmentation, and formation of membrane-enveloped apoptotic bodies, that are rapidly phagocytosed by macrophages or neighboring cells. Neurodegenerative disorders are becoming increasingly prevalent, especially in the Western societies, with larger percentage of members living to an older age. They have to be seen not only as a health problem, but since they are care-intensive, they also carry a significant economic burden. Deregulation of autophagy plays a pivotal role in the etiology and/or progress of many of these diseases. Herein, we briefly review the latest findings that indicate the involvement of autophagy in neurodegenerative diseases. We provide a brief introduction to autophagy and apoptosis pathways focusing on the role of mitochondria and lysosomes. We then briefly highlight pathophysiology of common neurodegenerative disorders like Alzheimer's diseases, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Then, we describe functions of autophagy and apoptosis in brain homeostasis, especially in the context of the aforementioned disorders. Finally, we discuss different ways that autophagy and apoptosis modulation may be employed for therapeutic intervention during the maintenance of neurodegenerative disorders.

Place, publisher, year, edition, pages
Kidlington, Oxford, United Kingdom: Pergamon Press, 2014
National Category
Biological Sciences
Identifiers
urn:nbn:se:liu:diva-99887 (URN)10.1016/j.pneurobio.2013.10.004 (DOI)000330911300002 ()
Available from: 2013-10-22 Created: 2013-10-22 Last updated: 2019-01-22
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5914-2837

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