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N.Ekdahl, K., Fromell, K., Mohlin, C., Teramura, Y. & Nilsson, B. (2019). A human whole-blood model to study the activation of innate immunity system triggered by nanoparticles as a demonstrator for toxicity. Science and Technology of Advanced Materials, 20(1), 688-698
Open this publication in new window or tab >>A human whole-blood model to study the activation of innate immunity system triggered by nanoparticles as a demonstrator for toxicity
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2019 (English)In: Science and Technology of Advanced Materials, ISSN 1468-6996, E-ISSN 1878-5514, Vol. 20, no 1, p. 688-698Article, review/survey (Refereed) Published
Abstract [en]

In this review article, we focus on activation of the soluble components of the innate immune system triggered by nonbiological compounds and stress variances in activation due to the difference in size between nanoparticles (NPs) and larger particles or bulk material of the same chemical and physical composition. We then discuss the impact of the so-called protein corona which is formed on the surface of NPs when they come in contact with blood or other body fluids. For example, NPs which bind inert proteins, proteins which are prone to activate the contact system (e.g., factor XII), which may lead to clotting and fibrin formation or the complement system (e.g., IgG or C3), which may result in inflammation and vascular damage. Furthermore, we describe a whole blood model which we have developed to monitor activation and interaction between different components of innate immunity: blood protein cascade systems, platelets, leukocytes, cytokine generation, which are induced by NPs. Finally, we describe our own studies on innate immunity system activation induced by three fundamentally different species of NPs (two types of engineered NPs and diesel NPs) as demonstrator of the utility of an initial determination of the composition of the protein corona formed on NPs exposed to ethylenediaminetetraacetic acid (EDTA) plasma and subsequent analysis in our whole blood model. [GRAPHICS] .

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Coagulation system, complement system, contact, kallikrein system, inflammation, innate immunity, nanoparticles, protein corona, screening, toxicity, whole blood model
National Category
Pharmacology and Toxicology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-390411 (URN)10.1080/14686996.2019.1625721 (DOI)000472611100001 ()31275460 (PubMedID)
Funder
Swedish Research Council, 2016-20755-1Swedish Research Council, 2016-04519Swedish Research Council, 2018-04199
Available from: 2019-08-12 Created: 2019-08-12 Last updated: 2019-08-12Bibliographically approved
Noiri, M., Kushiro, K., Togo, S., Sato, K., Yoshikawa, H. Y., Takai, M. & Teramura, Y. (2019). Influence of cell adhesive molecules attached onto PEG-lipid-modified fluid surfaces on cell adhesion. Colloids and Surfaces B: Biointerfaces, 175, 375-383
Open this publication in new window or tab >>Influence of cell adhesive molecules attached onto PEG-lipid-modified fluid surfaces on cell adhesion
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2019 (English)In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 175, p. 375-383Article in journal (Refereed) Published
Abstract [en]

The involvement of intercellular interactions in various biological events indicates the importance of studying cell-cell interactions using fluid model surfaces. Here, we propose a fluid surface composed of a self-assembled monolayer (SAM) and poly(ethylene glycol)-conjugated phospholipid (PEG-lipid) derivatives, which can be an alternative to supported lipid membranes. The modification of SAM surfaces with PEG-lipids carrying functional peptides resulted in the formation of the fluid surfaces with different mobility, which was quantitatively determined by quartz crystal microbalance with dissipation (QCM-D) and fluorescence recovery after photobleaching (FRAP). Different types of fluid surfaces with calculated diffusion coefficients between 0.9 ± 0.25 and 0.16 ± 0.03 μm2/sec for PEG-lipids derivatives were fabricated, onto which arginylglycylaspartate (RGD) peptides were immobilized for cell adhesion, and compared to solid surfaces with the same surface density of RGD peptides. The fluid surfaces revealed that cell adhesions of epithelial cells (MCF-10 A) and human umbilical vein endothelial cells (HUVEC) could not be established on the surfaces with higher fluidity, while cells could adhere onto surfaces with lower fluidity, where the lateral diffusion of PEG-lipids was approximately 20 times lower, and solid surfaces. Interestingly, cells that adhered onto the surface with lower fluidity proliferated at a normal rate while maintaining their round morphology, which was a different shape from that observed on solid surfaces. Thus, the scaffold fluidity greatly influenced cell adhesion behaviors, demonstrating that it is an important parameter for designing novel biomimetic scaffolds for biomedical applications.

Keywords
Poly(ethylene glycol)-conjugated phospholipid (PEG-lipid), RGD, Fluid surface, Cell adhesion
National Category
Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-379338 (URN)10.1016/j.colsurfb.2018.12.015 (DOI)000459837800043 ()30554016 (PubMedID)
Funder
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)
Available from: 2019-03-15 Created: 2019-03-15 Last updated: 2019-03-15Bibliographically approved
Noiri, M., Asawa, K., Okada, N., Kodama, T., Murayama, Y., Inoue, Y., . . . Teramura, Y. (2019). Modification of human MSC surface with oligopeptide-PEG-lipids for selective binding to activated endothelium. Journal of Biomedical Materials Research. Part A, 107(8), 1779-1792
Open this publication in new window or tab >>Modification of human MSC surface with oligopeptide-PEG-lipids for selective binding to activated endothelium
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2019 (English)In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 107, no 8, p. 1779-1792Article in journal (Refereed) Published
Abstract [en]

Promising cell therapies using mesenchymal stem cells (MSCs) is proposed for stroke patients. Therefore, we aimed to efficiently accumulate human MSC (hMSC) to damaged brain area to improve the therapeutic effect using poly(ethylene glycol) (PEG)-conjugated phospholipid (PEG-lipid) carrying an oligopeptide as a ligand, specific for E-selectin which is upregulated on activated endothelial cells under hypoxia-like stroke. Here we synthesized E-selectin-binding oligopeptide (ES-bp) conjugated with PEG spacer having different molecular weights from 1 to 40 kDa. We found that ES-bp can be immobilized onto the hMSC surface through PEG-lipid without influence on cell growth and differentiation into adipocytes and osteocytes, respectively. It is also possible to control the immobilization of ES-bp on hMSC surface (<10(8) ES-bp per cell). Immobilized ES-bp can be continuously immobilized at the outside of cell membrane when PEG-lipids with PEG 5 and 40 kDa were used. In addition, the modified hMSC can specifically attach onto E-selectin-immobilized surface as a model surface of activated endothelium in human blood, indicating the sufficient number of immobilized ES-bp onto hMSC. Thus, this technique is one of the candidates for hMSC accumulation to cerebral infarction area.

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
cell surface modification, E-selectin, mesenchymal stem cell (MSC), poly(ethylene glycol)-conjugated phospholipid (PEG-lipid), stroke
National Category
Biomaterials Science
Identifiers
urn:nbn:se:uu:diva-390077 (URN)10.1002/jbm.a.36697 (DOI)000471813900020 ()30983125 (PubMedID)
Funder
Swedish Research Council, 2016-2075-5.1Swedish Research Council, 2016-04519
Available from: 2019-08-06 Created: 2019-08-06 Last updated: 2019-08-06Bibliographically approved
Asif, S., Asawa, K., Yuuki, I., Ishihara, K., Lindell, B., Holmgren, R., . . . Nilsson Ekdahl, K. (2019). Validation of an MPC polymer coating to attenuate surface- induced cross-talk between the complement and coagulation systems in whole blood in in vitro and in vivo models. Macromolecular Bioscience, 19(5), Article ID 1800485.
Open this publication in new window or tab >>Validation of an MPC polymer coating to attenuate surface- induced cross-talk between the complement and coagulation systems in whole blood in in vitro and in vivo models
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2019 (English)In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 19, no 5, article id 1800485Article in journal (Refereed) Published
Abstract [en]

Artificial surfaces that come into contact with blood induce an immediate activation of the cascade systems of the blood, leading to a thrombotic and/or inflammatory response that can eventually cause damage to the biomaterial or the patient, or to both. Heparin coating has been used to improve hemocompatibility, and another approach is 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer coatings. Here, the aim is to evaluate the hemocompatibility of MPC polymer coating by studying the interactions with coagulation and complement systems using human blood in vitro model and pig in vivo model. The stability of the coatings is investigated in vitro and MPC polymer-coated catheters are tested in vivo by insertion into the external jugular vein of pigs to monitor the catheters' antithrombotic properties. There is no significant activation of platelets or of the coagulation and complement systems in the MPC polymer-coated one, which was superior in hemocompatibility to non-coated matrix surfaces. The protective effect of the MPC polymer coat does not decline after incubation in human plasma for up to 2 weeks. With MPC polymer-coated catheters, it is possible to easily draw blood from pig for 4 days in contrast to the case for non-coated catheters, in which substantial clotting is seen.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2019
Keywords
blood compatibility, blood model systems, coagulation system, complement system, heparin coat, MPC polymer coat
National Category
Clinical Laboratory Medicine Biomaterials Science
Identifiers
urn:nbn:se:uu:diva-374785 (URN)10.1002/mabi.201800485 (DOI)000471340300015 ()30786149 (PubMedID)
Funder
Swedish Research Council, 2016-2075-5.1Swedish Research Council, 2016-04519The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)
Note

Kazuhiko Ishihara har tillkommit som författare sedan posten lades in som manuskript.

Available from: 2019-01-24 Created: 2019-01-24 Last updated: 2019-07-31Bibliographically approved
Yoshihara, A., Sekine, R., Ueki, T., Kondo, Y., Sunaga, Y., Nakaji-Hirabayashi, T., . . . Takai, M. (2018). Rapid and highly efficient capture and release of cancer cells using polymeric microfibers immobilized with enzyme-cleavable peptides. Acta Biomaterialia, 67, 32-41
Open this publication in new window or tab >>Rapid and highly efficient capture and release of cancer cells using polymeric microfibers immobilized with enzyme-cleavable peptides
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2018 (English)In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 67, p. 32-41Article in journal (Refereed) Published
Abstract [en]

Circulating tumor cells (CTCs) are tumor cells present in the blood. CTCs have attracted much attention as a new tumor marker, because their analysis provides useful information for monitoring cancer progress. In this study, we developed cell-capture and release methods using three-dimensional (3D) microfiber fabrics without damaging the cells. Using functional peptides containing sequences from a polystyrene-binding site and a cleavable site for collagenase type IV, immobilized antibodies on the peptides were able to specifically capture MCF-7 cells in a few minutes and release the captured cells from 3D microfiber fabrics incorporating a vacuum system. The efficiency of cell capture was around 80% and that of the cell release was over 90%. The released cells proliferated normally in culture medium, suggesting that our system will be applicable for the culture and analysis of CTCs. Statement of Significance In this paper, we report cell-capture and release methods using enzyme-cleavable peptides immobilized on microfiber fabrics which has microporous polymeric three-dimensional structures. Detachment and collection of the selectively captured cancer cells are required for ex vivo culture and their further analysis, whereas the cell detachment methods developed so far might cause cell damage, even if cell viability is high enough. Therefore, specific attachment and gentle detachment from the device are required for the accurate analysis of cells. In this study, for capture and release of cancer cells we designed the peptide cleavable by collagenase type IV, which has no target molecule in cells. Our system will be useful for further CTC analysis and might lead to more accurate cancer diagnosis.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
Keywords
Circulating tumor cell, CTC, Microfiber fabric, Epithelial cell adhesion molecule, EpCAM, Polystyrene-binding peptide, Collagenase-cleavable sequence
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-351018 (URN)10.1016/j.actbio.2017.11.055 (DOI)000424853600003 ()29223702 (PubMedID)
Available from: 2018-05-24 Created: 2018-05-24 Last updated: 2018-05-24Bibliographically approved
Ogasawara, H., Teramura, Y., Imura, T., Inagaki, A., Saito, Y., Matsumura, M., . . . Goto, M. (2018). The Optimization of the Hepatocyte Surface Modification Procedures in Terms of Heparin and Apyrase for Improving Hepatocyte Engraftment. Paper presented at 14th World Congress of the International-Pancreas-and-Islet-Transplant-Association (IPITA), SEP 24-27, 2013, Monterey, CA. Transplantation, 102, S727-S727
Open this publication in new window or tab >>The Optimization of the Hepatocyte Surface Modification Procedures in Terms of Heparin and Apyrase for Improving Hepatocyte Engraftment
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2018 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 102, p. S727-S727Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2018
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-368383 (URN)10.1097/01.tp.0000543706.60801.e9 (DOI)000444541201427 ()
Conference
14th World Congress of the International-Pancreas-and-Islet-Transplant-Association (IPITA), SEP 24-27, 2013, Monterey, CA
Available from: 2018-12-06 Created: 2018-12-06 Last updated: 2018-12-06Bibliographically approved
Nilsson, B., Asif, S., Ekdahl N., K., Manell, E., Biglarnia, A., Jensen-Waern, M. & Teramura, Y. (2017). A protective role of complement regulators linked to a PEG phospholipid construct in reducing ischemic reperfusion injury in transplantation. Paper presented at 16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK. Molecular Immunology, 89, 208-208
Open this publication in new window or tab >>A protective role of complement regulators linked to a PEG phospholipid construct in reducing ischemic reperfusion injury in transplantation
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2017 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, p. 208-208Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD, 2017
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-377095 (URN)10.1016/j.molimm.2017.06.214 (DOI)000410014500195 ()
Conference
16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK
Available from: 2019-02-14 Created: 2019-02-14 Last updated: 2019-02-14Bibliographically approved
Teramura, Y., Asif, S., Nilsson Ekdahl, K., Gustafson, E. K. & Nilsson, B. (2017). Cell Adhesion Induced Using Surface Modification with Cell-Penetrating Peptide-Conjugated Poly(ethylene glycol)-Lipid: A New Cell Glue for 3D Cell-Based Structures. ACS Applied Materials and Interfaces, 9(1), 244-254
Open this publication in new window or tab >>Cell Adhesion Induced Using Surface Modification with Cell-Penetrating Peptide-Conjugated Poly(ethylene glycol)-Lipid: A New Cell Glue for 3D Cell-Based Structures
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2017 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 9, no 1, p. 244-254Article in journal (Refereed) Published
Abstract [en]

We synthesized a novel material, cell-penetrating peptide-conjugated poly(ethylene glycol)-lipid (CPP-PEG-lipid), that can induce the adhesion of floating cells. Firm cell adhesion with spreading could be induced by cell surface modification with the CPP-PEG-lipids. Cell adhesion was induced by CPPs but not by any other cationic short peptides we tested. Here, we demonstrated adherence using the floating cell line CCRF-CEM as well as primary human T cells, B cells, erythrocytes, and hepatocytes. As compared to cells grown in suspension, adherent cells were more rapidly induced to attach to substrates with the cell-surface modification. The critical factor for attachment was localization of CPPs at the cell membrane by PEG-lipids with PEG > 20 kDa. These cationic CPPs on PEG chains were able to interact with substrate surfaces such as polystyrene (PS) surfaces, glass surfaces, and PS microfibers that are negatively charged, inducing firm cell adhesion and cell spreading. Also, as opposed to normal cationic peptides that interact strongly with cell membranes, CPPs were less interactive with the cell surfaces because of their cell-penetrating property, making them more available for adhering cells to the substrate surface. No effects on cell viability or cell proliferation were observed after the induction of cell adhesion. With this technique, cells could be easily immobilized onto PS microfibers, an important step in fabricating 3D cell-based structures. Cells immobilized onto 3D PS microfibers were alive, and human hepatocytes showed normal production of urea and albumin on the microfibers. This method is novel in inducing firm cell adhesion via a one-step treatment.

Keywords
3D structure, cell adhesion, cell surface modification, cell-penetrating peptide (CPP), poly(ethylene glycol)-conjugated phospholipid (PEG−lipid)
National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-373991 (URN)10.1021/acsami.6b14584 (DOI)000392037400031 ()27976850 (PubMedID)
Funder
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)
Available from: 2019-01-17 Created: 2019-01-17 Last updated: 2019-01-24Bibliographically approved
Azuma, T., Ohmori, R., Teramura, Y., Ishizaki, T. & Takai, M. (2017). Nano-structural comparison of 2-methacryloyloxyethyl phosphorylcholine- and ethylene glycol-based surface modification for preventing protein and cell adhesion. Colloids and Surfaces B: Biointerfaces, 159, 655-661
Open this publication in new window or tab >>Nano-structural comparison of 2-methacryloyloxyethyl phosphorylcholine- and ethylene glycol-based surface modification for preventing protein and cell adhesion
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2017 (English)In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 159, p. 655-661Article in journal (Refereed) Published
Abstract [en]

Polymer brush, owing to its precisely controllable nanostructure, has great potential for surface modification in the biomedical field. In this study, we evaluated the bio-inertness of polymer brush, monomer monolayers, and polymer-coated surfaces based on their structures, to identify the most effective bio-inert modification. We focused on two well-known bio-inert materials, 2-methacryloyloxyethyl phosphorylcholine (MPC) and ethylene glycol (EG). The amount of adsorbed proteins on the surface was found to be dependent on the monomer unit density in the case of MPC, whereas this correlation was not observed in the case of EG. Cell adhesion was suppressed on the brush structure of both MPC and EG units, regardless of their density. The brush structure of MPC and EG units showed better anti-protein and anti-cell-adhesion than monolayers and polymer-coated surfaces. Thus, the steric repulsion was not only important in EG units-based surface, but also in MPC-based surface. In addition, multiple polymer layers formed by MPC-based polymer coating also displayed similar properties. (C) 2017 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
MPC polymer, PEG, Polymer brush, Polymer coating, Monolayer, Cell adhesion
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-339698 (URN)10.1016/j.colsurfb.2017.08.039 (DOI)000418729600076 ()28866413 (PubMedID)
Available from: 2018-01-29 Created: 2018-01-29 Last updated: 2018-01-29Bibliographically approved
Ohgaki, R., Teramura, Y., Hayashi, D., Quan, L., Okuda, S., Nagamori, S., . . . Kanai, Y. (2017). Ratiometric fluorescence imaging of cell surface pH by poly(ethylene glycol)-phospholipid conjugated with fluorescein isothiocyanate. Scientific Reports, 7, Article ID 17484.
Open this publication in new window or tab >>Ratiometric fluorescence imaging of cell surface pH by poly(ethylene glycol)-phospholipid conjugated with fluorescein isothiocyanate
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 17484Article in journal (Refereed) Published
Abstract [en]

Various physiological and pathological processes are accompanied with the alteration of pH at extracellular juxtamembrane region. Accordingly, the methods to analyze the cell surface pH have been demanded in biological and medical sciences. In this study, we have established a novel methodology for cell surface pH imaging using poly(ethylene glycol)-phospholipid (PEG-lipid) as a core structure of ratiometric fluorescent probes. PEG-lipid is a synthetic amphiphilic polymer originally developed for the cell surface modification in transplantation therapy. Via its hydrophobic alkyl chains of the phospholipid moiety, PEG-lipid is, when applied extracellularly, spontaneously inserted into the plasma membrane and retained at the surface of the cells. We have demonstrated that the PEG-lipid conjugated with fluorescein isothiocyanate (FITC-PEG-lipid) can be used as a sensitive and reversible cell-surfacea-nchored pH probe between weakly alkaline and acidic pH with an excellent spatiotemporal resolution. The remarkably simple procedure for cell-surface labeling with FITC-PEG-lipid would also be advantageous when considering its application to high-throughput in vitro assay. This study further indicates that various probes useful for the investigation of juxtamembrane environments could also be developed by using PEG-lipid as the core structure for bio-membrane anchoring.

National Category
Cell and Molecular Biology Other Basic Medicine
Identifiers
urn:nbn:se:uu:diva-339795 (URN)10.1038/s41598-017-17459-y (DOI)000417796000004 ()29235482 (PubMedID)
Available from: 2018-03-02 Created: 2018-03-02 Last updated: 2018-03-02Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-0709-1000

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