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Ivarsson, Mikael
Publications (10 of 11) Show all publications
Ivarsson, M., Prenkert, M., Cheema, A., Wretenberg, P. & Andjelkov, N. (2019). Mussel Adhesive Protein as a Promising Alternative to Fibrin for Scaffold Fixation during Cartilage Repair Surgery. Cartilage, Article ID 1947603519887319.
Open this publication in new window or tab >>Mussel Adhesive Protein as a Promising Alternative to Fibrin for Scaffold Fixation during Cartilage Repair Surgery
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2019 (English)In: Cartilage, ISSN 1947-6035, E-ISSN 1947-6043, article id 1947603519887319Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE: Fibrin has been used as a standard material for scaffold fixation during cartilage repair surgery. Most of the commercially available fibrin preparations need an additional method for scaffold fixation, most often with sutures, thus damaging the surrounding healthy cartilage. There is therefore a need to find alternatives to this method. In our study, we have investigated the potential possibility to use mussel adhesive protein as such an alternative.

METHODS: In this study, hydrophobic plastic was coated with the mussel adhesive protein Mefp-1 as well as with other cell adhesives (poly-lysine, fibronectin, and collagen). Human keratinocytes and chondrocytes were seeded on these substrates at 37°C in culture medium, followed by analysis of attachment and proliferation by crystal violet staining and metabolic labelling. Performance of Mefp-1 and fibrin as tissue glues were estimated by tensional force resistance measurement of moist porcine dermis (as a correlate to scaffold) glued to dermis, cartilage, or bone at 37°C.

RESULTS: Mefp-1 supported maximal cell attachment at a coating density of approximately 1 µg/cm2. This was at least as good as the other adhesives tested. In addition, it supported cell proliferation at least as good as regular tissue culture plastic over a 7-day period. Measurement of tensional force resistance showed that Mefp-1 performed equally well as fibrin when porcine dermis was glued to cartilage and bone at the same concentration. Separation of the moist tissues after 15-minute incubation required a force of approximately 1 N/cm2 for both compounds.

CONCLUSIONS: Mefp-1 show properties that qualify it as a compound that potentially could replace fibrin as a tissue glue for scaffold fixation. Given the possibilities to modify this protein by bioengineering, it is likely that the properties can be further improved.

Place, publisher, year, edition, pages
Sage Publications, 2019
Keywords
articular cartilage, biomaterials, scaffolds
National Category
Surgery
Identifiers
urn:nbn:se:oru:diva-77978 (URN)10.1177/1947603519887319 (DOI)000497303600001 ()31729255 (PubMedID)
Funder
Knowledge Foundation, 20120179
Note

Funding Agency:

Örebro University

Available from: 2019-11-20 Created: 2019-11-20 Last updated: 2019-12-10Bibliographically approved
Åström, M., Welander, E., Pourlotfi, A., Abawi, A., Ahlstrand, E. & Ivarsson, M. (2018). Activated interferon signaling in cultured BMSC from myelofibrosis patients: core finding of a proteomic study. In: : . Paper presented at 2nd International Conference on Tissue Repair, Regeneration, and Fibrosis, Chania, Crete, Greece, June 13-16, 2018.
Open this publication in new window or tab >>Activated interferon signaling in cultured BMSC from myelofibrosis patients: core finding of a proteomic study
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:oru:diva-67255 (URN)
Conference
2nd International Conference on Tissue Repair, Regeneration, and Fibrosis, Chania, Crete, Greece, June 13-16, 2018
Available from: 2018-06-14 Created: 2018-06-14 Last updated: 2018-06-14Bibliographically approved
Welander, E., Åström, M., Enonge Fotabe, L., Kardeby, C., Tina, E., Elgbratt, K., . . . Ivarsson, M. (2018). Integrated analysis indicates reciprocal immune response dysregulations between bone marrow multipotent stromal cells and granulocytes at the mRNA but not at the protein level in myelofibrosis. In: : . Paper presented at Fortbildningsdagar i hematologi, Umeå, 3-5 Oktober, 2018.
Open this publication in new window or tab >>Integrated analysis indicates reciprocal immune response dysregulations between bone marrow multipotent stromal cells and granulocytes at the mRNA but not at the protein level in myelofibrosis
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-69350 (URN)
Conference
Fortbildningsdagar i hematologi, Umeå, 3-5 Oktober, 2018
Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2019-03-26Bibliographically approved
Koskela von Sydow, A., Janbaz, C., Kardeby, C., Repsilber, D. & Ivarsson, M. (2016). IL-1α Counteract TGF-β Regulated Genes and Pathways in Human Fibroblasts. Journal of Cellular Biochemistry, 117(7), 1622-1632
Open this publication in new window or tab >>IL-1α Counteract TGF-β Regulated Genes and Pathways in Human Fibroblasts
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2016 (English)In: Journal of Cellular Biochemistry, ISSN 0730-2312, E-ISSN 1097-4644, Vol. 117, no 7, p. 1622-1632Article in journal (Refereed) Published
Abstract [en]

Dysregulated wound healing is commonly associated with excessive fibrosis. Connective tissue growth factor (CTGF/CCN2) is characteristically overexpressed in fibrotic diseases and stimulated by transforming growth factor-β (TGF-β) in dermal fibroblasts. We previously showed that interleukin-1 (IL-1α) counteracts TGF-β-stimulated CTGF mRNA and protein expression in these cells. The aim of this study was to explore the effects of IL-1α on further genes and pathways in TGF-β regulated fibroblasts. Transcriptional microarray and multiple comparison analysis showed that the antagonizing effects of IL-1α was much more prominent than the synergistic effects, both with respect to number of genes and extent of changes in gene expression. Moreover, comparing canonical pathways by gene set enrichment analysis and the Ingenuity Pathway Analysis tool revealed that IL-1α counteracted TGF-β in the top six most confident pathways regulated by both cytokines. Interferon and IL-1 signaling, as well as two pathways involved in apoptosis signaling were suppressed by TGF-β and activated by IL-1α. Pathways involving actin remodeling and focal adhesion dynamics were activated by TGF-β and suppressed by IL-1α. Analyzing upstream regulators in part corroborate the comparison of canonical pathways and added cell cycle regulators as another functional group regulated by IL-1α. Finally, gene set enrichment analysis of fibrosis-related genes indicated that IL-1 moderately counteracts the collective effect of TGF-β on these genes. Microarray results were validated by qPCR. Taken together, the results indicate prominent antagonistic effects of IL-1α on TGF-β regulated interferon signaling, as well as on a wide variety of other genes and pathways in fibroblasts. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell, 2016
Keywords
Connective tissue growth factor, transforming growth factor-beta, interleukin-1, interferon, fibroblast, fibrosis and ingenuity pathway analysis
National Category
Other Basic Medicine Cell Biology Biochemistry and Molecular Biology
Research subject
Cell Research
Identifiers
urn:nbn:se:oru:diva-48463 (URN)10.1002/jcb.25455 (DOI)000375916800014 ()26629874 (PubMedID)2-s2.0-84964773875 (Scopus ID)
Note

Funding Agencies:

Örebro County Council Research Committee of the Örebro University Hospital OLL-550071

Nyckelfonden AE56340

Available from: 2016-02-22 Created: 2016-02-22 Last updated: 2019-03-26Bibliographically approved
Landström, F., Ivarsson, M., von Sydow, A. K., Magnuson, A., von Beckerath, M. & Möller, C. (2015). Electrochemotherapy: Evidence for Cell-type Selectivity In Vitro. Anticancer Research, 35(11), 5813-5820
Open this publication in new window or tab >>Electrochemotherapy: Evidence for Cell-type Selectivity In Vitro
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2015 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 11, p. 5813-5820Article in journal (Refereed) Published
Abstract [en]

Aim: Electrochemotherapy (ECT) is a new cancer treatment modality that uses electroporation to potentiate chemotherapeutic agents, especially bleomycin. ECT causes both a direct toxic effect and an anti-vascular effect. The aim of the present study was to investigate a possible selective effect of ECT on the survival of fibroblasts, endothelial cells (HUVEC) and two squamous cell carcinoma cell lines (CAL-27 and SCC-4).

Materials and Methods: Cells were electroporated using two bleomycin concentrations. The survival rate was assessed 1, 2, 3 and 4 days after treatment, by two different assays.

Results: The survival rate of the fibroblasts was statistically significantly higher than the other cell lines at day 4. The HUVEC survival rate was statistically significantly lower than the other cell types at day 1 after electroporation-alone.

Conclusion: A selective survival effect after ECT was observed in vitro, supporting the anti-vascular effect seen in vivo.

Place, publisher, year, edition, pages
International Institute of Anticancer Research, 2015
Keywords
Electrochemotherapy, bleomycin, head and neck cancer, squamous cell carcinoma, fibroblasts, endothelial cells, selectivity
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-46832 (URN)000363794900010 ()26504002 (PubMedID)2-s2.0-84946055559 (Scopus ID)
Note

Funding Agency:

Örebro County Council

Available from: 2015-11-27 Created: 2015-11-27 Last updated: 2018-07-02Bibliographically approved
Ivarsson, M., Schollin, J. & Björkqvist, M. (2013). Staphylococcus epidermidis and Staphylococcus aureus trigger different interleukin-8 and intercellular adhesion molecule-1 in lung cells: implications for inflammatory complications following neonatal sepsis. Acta Paediatrica, 102(10), 1010-1016
Open this publication in new window or tab >>Staphylococcus epidermidis and Staphylococcus aureus trigger different interleukin-8 and intercellular adhesion molecule-1 in lung cells: implications for inflammatory complications following neonatal sepsis
2013 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 10, p. 1010-1016Article in journal (Refereed) Published
Abstract [en]

Aim: Staphylococci are a major contribution for neonatal sepsis, which is the main risk factor for bronchopulmonary dysplasia. This study investigated the expression of pro-inflammatory mediators in endothelial and respiratory cells from newborns exposed to staphylococci.

Methods: Human vascular endothelial cells and small airway epithelial cells were incubated with neonatal blood isolates of Staphylococcus epidermidis (n = 14) and Staphylococcus aureus (n = 14). The extracellular release of IL-8, IL-10, sICAM-1, ICAM-1 mRNA and the expression of membrane bound ICAM-1 were assessed by ELISA, RT-PCR and immunofluorescence microscopy.

Results: Staphylococcus epidermidis induced higher levels of IL-8 (mean 38.5 ng/mL) and ICAM-1 mRNA (mean ratio 1.037) in the small airway epithelial cells than S. aureus (IL-8 mean 22.2 ng/mL, p < 0.01 and ICAM-1 mRNA mean ratio 0.715, p < 0.01). In the endothelial cells, ICAM-1 remained more integrated in the cell membranes after exposure to S. epidermidis compared with S. aureus, which induced disintegration and release of soluble ICAM-1 into the supernatants.

Conclusion: Staphylococcus epidermidis induced a higher chemoattractive response than S. aureus. A persistent transmigration of granulocytes into the lung tissue in neonatal S. epidermidis sepsis might contribute to the development of bronchopulmonary dysplasia.

Keywords
Bronchopulmonary dysplasia, ICAM-1, Interleukin-8, Neonatal sepsis, Staphylococci
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-31079 (URN)10.1111/apa.12350 (DOI)000323886300030 ()23845107 (PubMedID)
Available from: 2013-10-04 Created: 2013-10-04 Last updated: 2018-05-21Bibliographically approved
Nowinski, D., Koskela, A., Kiwanuka, E., Boström, M., Gerdin, B. & Ivarsson, M. (2010). Inhibition of Connective Tissue Growth Factor/CCN2 Expression in Human Dermal Fibroblasts by Interleukin-1 alpha and beta. Journal of Cellular Biochemistry, 110(5), 1226-1233
Open this publication in new window or tab >>Inhibition of Connective Tissue Growth Factor/CCN2 Expression in Human Dermal Fibroblasts by Interleukin-1 alpha and beta
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2010 (English)In: Journal of Cellular Biochemistry, ISSN 0730-2312, E-ISSN 1097-4644, Vol. 110, no 5, p. 1226-1233Article in journal (Refereed) Published
Abstract [en]

Connective tissue growth factor (CTGF/CCN2) is a matricellular protein induced by transforming growth factor (TGF)-beta and intimately involved with tissue repair and overexpressed in various fibrotic conditions We previously showed that keratmocytes in vitro downregulate TGF-beta-induced expression of CTGF in fibroblasts by an interleukin (IL)-1 alpha-dependent mechanism. Here, we investigated further the mechanisms of this downregulation by both IL-1 alpha and beta Human dermal fibroblasts and NIH 3T3 cells were treated with IL-1 alpha or beta in presence or absence of TGF-beta 1. IL-1 suppressed basal and TGF-beta-induced CTGF mRNA and protein expression. IL-1 alpha and beta inhibited TGF-beta-stimulated CTGF promoter activity, and the activity of a synthetic minimal promoter containing Smad 3-binding CAGA elements Furthermore. IL-1 alpha and beta inhibited TGF-beta-stimulated Smad 3 phosphorylation, possibly linked to an observed increase in Smad 7 mRNA expression. In addition. RNA interference suggested that TGF-beta activated kinase1 (TAK1) is necessary for IL-1 inhibition of TGF-beta-stimulated CTGF expression. These results add to the understanding of how the expression of CTGF in human dermal fibroblasts is regulated, which in turn may have implications for the pathogenesis of fibrotic conditions involving the skin. J. Cell Biochem. 110: 1226-1233, 2010. (C) 2010 Wiley-Liss. Inc

Keywords
interleukin-1, connective tissue growth factor, transforming growth factor-beta, smad 3, tak1
National Category
Cell Biology Biochemistry and Molecular Biology
Research subject
Cell Research
Identifiers
urn:nbn:se:oru:diva-28379 (URN)10.1002/jcb.22637 (DOI)000280435900021 ()20544797 (PubMedID)2-s2.0-77954894569 (Scopus ID)
Available from: 2013-03-26 Created: 2013-03-14 Last updated: 2018-04-24Bibliographically approved
Jimbo, R., Ivarsson, M., Koskela, A., Sul, Y.-T. & Johansson, C. B. (2010). Protein adsorption to surface chemistry and crystal structure modification of titanium surfaces. Journal of oral & maxillofacial research, 1(3), e3
Open this publication in new window or tab >>Protein adsorption to surface chemistry and crystal structure modification of titanium surfaces
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2010 (English)In: Journal of oral & maxillofacial research, ISSN 2029-283X, Vol. 1, no 3, p. e3-Article in journal (Refereed) Published
Abstract [en]

Objectives: To observe the early adsorption of extracellular matrix and blood plasma proteins to magnesium-incorporated titanium oxide surfaces, which has shown superior bone response in animal models.

Material and Methods: Commercially pure titanium discs were blasted with titanium dioxide (TiO2) particles (control), and for the test group, TiO2 blasted discs were further processed with a micro-arc oxidation method (test). Surface morphology was investigated by scanning electron microscopy, surface topography by optic interferometry, characterization by X-ray photoelectron spectroscopy (XPS), and by X-ray diffraction (XRD) analysis. The adsorption of 3 different proteins (fibronectin, albumin, and collagen type I) was investigated by an immunoblotting technique.

Results: The test surface showed a porous structure, whereas the control surface showed a typical TiO2 blasted structure. XPS data revealed magnesium-incorporation to the anodic oxide film of the surface. There was no difference in surface roughness between the control and test surfaces. For the protein adsorption test, the amount of albumin was significantly higher on the control surface whereas the amount of fibronectin was significantly higher on the test surface. Although there was no significant difference, the test surface had a tendency to adsorb more collagen type I.

Conclusions: The magnesium-incorporated anodized surface showed significantly higher fibronectin adsorption and lower albumin adsorption than the blasted surface. These results may be one of the reasons for the excellent bone response previously observed in animal studies.

National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-11603 (URN)10.5037/jomr.2010.1303 (DOI)
Available from: 2010-08-18 Created: 2010-08-18 Last updated: 2017-10-18Bibliographically approved
Koskela, A., Engström, K., Hakelius, M., Nowinski, D. & Ivarsson, M. (2010). Regulation of fibroblast gene expression by keratinocytes in organotypic skin culture provides possible mechanisms for the antifibrotic effect of reepithelialization.. Wound Repair and Regeneration, 18(5), 452-459
Open this publication in new window or tab >>Regulation of fibroblast gene expression by keratinocytes in organotypic skin culture provides possible mechanisms for the antifibrotic effect of reepithelialization.
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2010 (English)In: Wound Repair and Regeneration, ISSN 1067-1927, E-ISSN 1524-475X, Vol. 18, no 5, p. 452-459Article in journal (Refereed) Published
Abstract [en]

To investigate the mechanisms behind the antifibrotic effect associated with epidermal regeneration, the expression of 12 fibroblast genes important for the modulation of the extracellular matrix (ECM), as well as α-smooth muscle actin, was studied in a keratinocyte-fibroblast organotypic skin culture model. The study was performed over time during epidermal generation and in the presence or absence of the profibrotic factor transforming growth factor-β. the Presence of epidermal differentiation markers in the model was essentially coherent with that of native skin. Fibroblast gene expression was analyzed with real-time polymerase chain reaction after removal of the epidermal layer. After 2 days of air-exposed culture, 11 out of the 13 genes studied were significantly regulated by keratinocytes in the absence or presence of transforming growth factor-β. The regulation of connective tissue growth factor, collagen I and III, fibronectin, plasmin system regulators, matrix metalloproteinases and their inhibitors as well as α-smooth muscle actin was consistent with a suppression of ECM formation or contraction. Overall, the results support a view that keratinocytes regulate fibroblasts to act catabolically on the ECM in epithelialization processes. This provides possible mechanisms for the clinical observations that reepithelialization and epidermal wound coverage counteract excessive scar formation.

Place, publisher, year, edition, pages
The Wound Healing Society, 2010
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:oru:diva-48462 (URN)10.1111/j.1524-475X.2010.00605.x (DOI)000282263500004 ()20731800 (PubMedID)2-s2.0-77956625499 (Scopus ID)
Available from: 2016-02-22 Created: 2016-02-22 Last updated: 2018-05-02Bibliographically approved
Tsai, J. A., Andersson, M. K., Ivarsson, M., Granberg, B. & Stark, A. (2009). Effects of synovial fluid from aseptic prosthesis loosening on collagen production in osteoblasts. International Orthopaedics, 33(3), 873-877
Open this publication in new window or tab >>Effects of synovial fluid from aseptic prosthesis loosening on collagen production in osteoblasts
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2009 (English)In: International Orthopaedics, ISSN 0341-2695, E-ISSN 1432-5195, Vol. 33, no 3, p. 873-877Article in journal (Refereed) Published
Abstract [en]

Synovial fluid from a loose prosthesis may act as a vehicle for factors that regulate bone turnover. The effect of such synovial fluid on osteoblasts has been studied. Synovial fluid obtained from patients who underwent revision hip arthroplasty because of aseptic prosthesis loosening was studied regarding the effect on protein synthesis, procollagen I mRNA expression, the secretion of procollagen I carboxyterminal propeptide (PICP) and osteocalcin in MG63 osteoblasts. Protein synthesis was increased and procollagen I mRNA expression was decreased by synovial fluid from patients with prosthesis loosening. Synovial fluid stimulated the total PICP in cell medium, but there was no change after correction for cell protein content in the cells. Synovial fluid in patients with prosthesis loosening has a general stimulatory effect on collagen formation and osteoblast proliferation because of a stimulatory effect on cell growth. Aseptic prosthesis loosening may be associated with an increase in bone formation.

National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-19233 (URN)10.1007/s00264-008-0533-z (DOI)000267041000047 ()
Available from: 2011-10-05 Created: 2011-10-04 Last updated: 2017-12-08Bibliographically approved
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