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  • 1.
    Bose, Tanima
    et al.
    Leibniz Inst Neurobiol, D-39 Magdeburg, Germany.
    Cieślar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Silesian Tech Univ, Inst Automat Control, Biosyst Grp, PL-44100 Gliwice, Poland.
    Wiechec, Emilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Role of ion channels in regulating Ca2+ homeostasis during the interplay between immune and cancer cells.2015In: Cell Death and Disease, E-ISSN 2041-4889, Vol. 19, no 6, article id e1648Article, review/survey (Refereed)
    Abstract [en]

    Ion channels are abundantly expressed in both excitable and non-excitable cells, thereby regulating the Ca2+ influx and downstream signaling pathways of physiological processes. The immune system is specialized in the process of cancer cell recognition and elimination, and is regulated by different ion channels. In comparison with the immune cells, ion channels behave differently in cancer cells by making the tumor cells more hyperpolarized and influence cancer cell proliferation and metastasis. Therefore, ion channels comprise an important therapeutic target in anti-cancer treatment. In this review, we discuss the implication of ion channels in regulation of Ca2+ homeostasis during the crosstalk between immune and cancer cell as well as their role in cancer progression.

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    Bose et al
  • 2.
    Chaabane, Wiem
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Tunis University, Tunisia.
    Cieślar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Silesian University of Technology, Gliwice, Poland.
    El-Gazzah, Mohamed
    Tunis University, Tunisia.
    Jain, Mayur V.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Rzeszowska-Wolny, Joanna
    Silesian University of Technology, Gliwice, Poland.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Health Sciences.
    Stetefeld, Joerg
    University of Manitoba, Winnipeg, Canada.
    Ghavami, Saeid
    University of Manitoba, Winnipeg, Canada.
    Los, Marek
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Pomeranian Medical University, Szczecin, Poland.
    Human-Gyrovirus-Apoptin Triggers Mitochondrial Death Pathway—Nur77 is Required for Apoptosis Triggering: 2014In: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 16, no 9, p. 679-693Article in journal (Refereed)
    Abstract [en]

    The human gyrovirus derived protein Apoptin (HGV-Apoptin) a homologue of the chicken anemia virus Apoptin (CAV-Apoptin), a protein with high cancer cells selective toxicity, trigger apoptosis selectively in cancer cells. In this paper, we show that HGV-Apoptin acts independently from the death receptor pathway as it induces apoptosis in similar rates in Jurkat cells deficient in either FADD-function or caspase-8 (key players of the extrinsic pathway) and their parental clones. HGV-Apoptin induces apoptosis via the activation of the mitochondrial intrinsic pathway. It induces both mitochondrial inner and outer membrane permebilization, characterized by the loss of the mitochondrial potential and the release into cytoplasm of the pro-apoptotic molecules including apoptosis inducing factor (AIF) and cytochrome c. HGV-Apoptin acts via the apoptosome, as lack of expression of APAF1 in murine embryonic fibroblast strongly protected the cells from HGV-Apoptin-induced apoptosis. Moreover, QVD-oph a broad-spectrum caspase inhibitor delayed HGV-Apoptin-induced death. On the other hand, overexpression of the anti-apoptotic BCL-XL confers resistance to HGV-Apoptin induced cell death. In contrast, cells that lack the expression of the pro-apoptotic BAX and BAK are protected from HGV-Apoptin induced apoptosis. Furthermore, HGV-Apoptin acts independently from p53 signal but triggers the cytoplasmic translocation of Nur77. Taking together this data indicate that HGV-Apoptin acts through the mitochondrial pathway, in a caspase-dependent manner but independently from the death receptor pathway.

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    14_Chaabane_HGyVapoptin_NeoplasiaGalley.pdf
  • 3.
    Cieslar-Pobuda, Artur
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Bäck, Marcus
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Magnusson, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Vilas Jain, Mayur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Health Sciences.
    Ghavami, Saeid
    Manitoba Institute Child Heatlh, Canada; University of Manitoba, Canada .
    Nilsson, Peter R.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Los, Marek Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Cell Type Related Differences in Staining with Pentameric Thiophene Derivatives2014In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 85A, no 7, p. 628-635Article in journal (Refereed)
    Abstract [en]

    Fluorescent compounds capable of staining cells selectively without affecting their viability are gaining importance in biology and medicine. Recently, a new family of optical dyes, denoted luminescent conjugated oligothiophenes (LCOs), has emerged as an interesting class of highly emissive molecules for studying various biological phenomena. Properly functionalized LCOs have been utilized for selective identification of disease-associated protein aggregates and for selective detection of distinct cells. Herein, we present data on differential staining of various cell types, including cancer cells. The differential staining observed with newly developed pentameric LCOs is attributed to distinct side chain functionalities along the thiophene backbone. Employing flow cytometry and fluorescence microscopy we examined a library of LCOs for stainability of a variety of cell lines. Among tested dyes we found promising candidates that showed strong or moderate capability to stain cells to different extent, depending on target cells. Hence, LCOs with diverse imidazole motifs along the thiophene backbone were identified as an interesting class of agents for staining of cancer cells, whereas LCOs with other amino acid side chains along the backbone showed a complete lack of staining for the cells included in the study. Furthermore, for p-HTMI,a LCO functionalized with methylated imidazole moieties, the staining was dependent on the p53 status of the cells, indicating that the molecular target for the dye is a cellular component regulated by p53. We foresee that functionalized LCOs will serve as a new class of optical ligands for fluorescent classification of cells and expand the toolbox of reagents for fluorescent live imaging of different cells.

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  • 4.
    Cieslar-Pobuda, Artur
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Wiechec-Los, Emilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Editorial Material: Research on liver regeneration as an answer to the shortage of donors for liver transplantation in HEPATOLOGY RESEARCH, vol 44, issue 9, pp 944-9462014In: Hepatology Research, ISSN 1386-6346, E-ISSN 1872-034X, Vol. 44, no 9, p. 944-946Article in journal (Other academic)
    Abstract [en]

    n/a

  • 5.
    Cieślar-Pobuda, Artur
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Biosystems Group, Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland.
    Los, Marek Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Department of Pathology, Pomeranian Medical University, Szczecin, Poland.
    Comments: Prospects and Limitations of“Click-Chemistry”-Based DNA LabelingTechnique Employing 5-Ethynyl-20deoxyuridine(EdU)2013In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 83, p. 977-978Article in journal (Other academic)
    Abstract [en]

    n/a

  • 6.
    Cieślar-Pobuda, Artur
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland.
    Vilas Jain, Mayur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Kratz, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Rzeszowska-Wolny, Joanna
    Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland.
    Ghavami, Saeid
    Department of Human Anatomy and Cell Science, University of Manitoba, Manitoba, Canada.
    Wiechec, Emilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    The expression pattern of PFKFB3 enzyme distinguishes between induced-pluripotent stem cells and cancer stem cells.2015In: Oncotarget, E-ISSN 1949-2553, Vol. 6, no 30, p. 29753--29770Article in journal (Refereed)
    Abstract [en]

    Induced pluripotent stem cells (iPS) have become crucial in medicine and biology. Several studies indicate their phenotypic similarities with cancer stem cells (CSCs) and a propensity to form tumors. Thus it is desirable to identify a trait which differentiates iPS populations and CSCs. Searching for such a feature, in this work we compare the restriction (R) point-governed regulation of cell cycle progression in different cell types (iPS, cancer, CSC and normal cells) based on the expression profile of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 (PFKFB3) and phosphofructokinase (PFK1). Our study reveals that PFKFB3 and PFK1 expression allows discrimination between iPS and CSCs. Moreover, cancer and iPS cells, when cultured under hypoxic conditions, alter their expression level of PFKFB3 and PFK1 to resemble those in CSCs. We also observed cell type-related differences in response to inhibition of PFKFB3. This possibility to distinguish CSC from iPS cells or non-stem cancer cells by PFKB3 and PFK1 expression improves the outlook for clinical application of stem cell-based therapies and for more precise detection of CSCs.

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  • 7.
    Gelmi, Amy
    et al.
    Linköping University, Faculty of Science & Engineering. Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Imperial Coll London, England.
    Cieslar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Silesian Technical University, Poland.
    de Muinck, Ebo
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Los, Marek Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Pomeranian Medical University, Poland.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering2016In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 5, no 12, p. 1471-1480Article in journal (Refereed)
    Abstract [en]

    The combination of stem cell therapy with a supportive scaffold is a promising approach to improving cardiac tissue engineering. Stem cell therapy can be used to repair nonfunctioning heart tissue and achieve myocardial regeneration, and scaffold materials can be utilized in order to successfully deliver and support stem cells in vivo. Current research describes passive scaffold materials; here an electroactive scaffold that provides electrical, mechanical, and topographical cues to induced human pluripotent stem cells (iPS) is presented. The poly(lactic-co-glycolic acid) fiber scaffold coated with conductive polymer polypyrrole (PPy) is capable of delivering direct electrical and mechanical stimulation to the iPS. The electroactive scaffolds demonstrate no cytotoxic effects on the iPS as well as an increased expression of cardiac markers for both stimulated and unstimulated protocols. This study demonstrates the first application of PPy as a supportive electroactive material for iPS and the first development of a fiber scaffold capable of dynamic mechanical actuation.

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  • 8.
    Gelmi, Amy
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Zhang, Jiabin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Cieslar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ljunggren, Monika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Los, Marek
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Medicine and Health Sciences.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Electroactive polymer scaffolds for cardiac tissue engineering2015In: Proc. SPIE 9430, Electroactive Polymer Actuators and Devices (EAPAD) 2015 / [ed] Bar-Cohen, SPIE - International Society for Optical Engineering, 2015, Vol. 9430, p. 94301T-1-94301T-7Conference paper (Refereed)
    Abstract [en]

    By-pass surgery and heart transplantation are traditionally used to restore the heart’s functionality after a myocardial Infarction (MI or heart attack) that results in scar tissue formation and impaired cardiac function. However, both procedures are associated with serious post-surgical complications. Therefore, new strategies to help re-establish heart functionality are necessary. Tissue engineering and stem cell therapy are the promising approaches that are being explored for the treatment of MI. The stem cell niche is extremely important for the proliferation and differentiation of stem cells and tissue regeneration. For the introduction of stem cells into the host tissue an artificial carrier such as a scaffold is preferred as direct injection of stem cells has resulted in fast stem cell death. Such scaffold will provide the proper microenvironment that can be altered electronically to provide temporal stimulation to the cells. We have developed an electroactive polymer (EAP) scaffold for cardiac tissue engineering. The EAP scaffold mimics the extracellular matrix and provides a 3D microenvironment that can be easily tuned during fabrication, such as controllable fibre dimensions, alignment, and coating. In addition, the scaffold can provide electrical and electromechanical stimulation to the stem cells which are important external stimuli to stem cell differentiation. We tested the initial biocompatibility of these scaffolds using cardiac progenitor cells (CPCs), and continued onto more sensitive induced pluripotent stem cells (iPS). We present the fabrication and characterisation of these electroactive fibres as well as the response of increasingly sensitive cell types to the scaffolds.

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  • 9.
    Jangamreddy, Jaganmohan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Ghavami, Saeid
    University of Manitoba, Winnipeg, Canada.
    Grabarek, Jerzy
    Pomeranian Medical University, Szczecin, Poland.
    Kratz, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Regenerative Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Wiechec, Emilia
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Department of Clinical and Experimental Medicine, Regenerative Medicine. Linköping University, Faculty of Health Sciences.
    Fredriksson, Bengt-Arne
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Rao, Rama K.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Cieślar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Department of Clinical and Experimental Medicine, Regenerative Medicine. Linköping University, Faculty of Health Sciences.
    Panigrahi, Soumya
    Lerner Research Institute, Cleveland, OH, USA.
    Łos, Marek
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Department of Clinical and Experimental Medicine, Regenerative Medicine. Linköping University, Faculty of Health Sciences.
    Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: Differences between primary and cancer cells2013In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1833, no 9, p. 2057-2069Article in journal (Refereed)
    Abstract [en]

    The molecular mechanism of Salinomycin's toxicity is not fully understood. Various studies reported that Ca2 +, cytochrome c, and caspase activation play a role in Salinomycin-induced cytotoxicity. Furthermore, Salinomycin may target Wnt/β-catenin signaling pathway to promote differentiation and thus elimination of cancer stem cells. In this study, we show a massive autophagic response to Salinomycin (substantially stronger than to commonly used autophagic inducer Rapamycin) in prostrate-, breast cancer cells, and to lesser degree in human normal dermal fibroblasts. Interestingly, autophagy induced by Salinomycin is a cell protective mechanism in all tested cancer cell lines. Furthermore, Salinomycin induces mitophagy, mitoptosis and increased mitochondrial membrane potential (∆Ψ) in a subpopulation of cells. Salinomycin strongly, and in time-dependent manner decreases cellular ATP level. Contrastingly, human normal dermal fibroblasts treated with Salinomycin show some initial decrease in mitochondrial mass, however they are largely resistant to Salinomycin-triggered ATP-depletion. Our data provide new insight into the molecular mechanism of preferential toxicity of Salinomycin towards cancer cells, and suggest possible clinical application of Salinomycin in combination with autophagy inhibitors (i.e. clinically-used Chloroquine). Furthermore, we discuss preferential Salinomycins toxicity in the context of Warburg effect.

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  • 10.
    Magnusson, Karin
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Appelqvist, Hanna
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Cieslar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Institute of Automatic Control, Silesian University of of TechnologyGliwice, Poland.
    Wigenius, Jens
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology. Carl Zeiss AB, Sweden.
    Karlsson, Thommie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Application Specialist Confocal Microscopy at Leica MicrosystemsIL, United States.
    Los, Marek Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Department of Pathology, Pomeranian Medical UniversitySzczecin, Poland.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Jonasson, Jon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte2015In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 87, no 3, p. 262-272Article in journal (Refereed)
    Abstract [en]

    Molecular probes for imaging of live cells are of great interest for studying biological and pathological processes. The anionic luminescent conjugated polythiophene (LCP) polythiophene acetic acid (PTAA), has previously been used for vital staining of cultured fibroblasts as well as transformed cells with results indicating differential staining due to cell phenotype. Herein, we investigated the behavior of PTAA in two normal and five transformed cells lines. PTAA fluorescence in normal cells appeared in a peripheral punctated pattern whereas the probe was more concentrated in a one-sided perinuclear localization in the five transformed cell lines. In fibroblasts, PTAA fluorescence was initially associated with fibronectin and after 24 h partially localized to lysosomes. The uptake and intracellular target in malignant melanoma cells was more ambiguous and the intracellular target of PTAA in melanoma cells is still elusive. PTAA was well tolerated by both fibroblasts and melanoma cells, and microscopic analysis as well as viability assays showed no signs of negative influence on growth. Stained cells maintained their proliferation rate for at least 12 generations. Although the probe itself was nontoxic, photoinduced cellular toxicity was observed in both cell lines upon irradiation directly after staining. However, no cytotoxicity was detected when the cells were irradiated 24 h after staining, indicating that the photoinduced toxicity is dependent on the cellular location of the probe. Overall, these studies certified PTAA as a useful agent for vital staining of cells, and that PTAA can potentially be used to study cancer-related biological and pathological processes.

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  • 11.
    Magnusson, Karin
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Appelqvist, Hanna
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Cieślar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Bäck, Marcus
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jonasson, Jon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Los, Marek J.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Peter R.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    An imidazole functionalized pentameric thiophene displays different staining patterns in normal and malignant cells2015In: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 3, article id 58Article in journal (Refereed)
    Abstract [en]

    Molecular tools for fluorescent imaging of cells and their components are vital for understanding the function and activity of cells. Here, we report an imidazole functionalized pentameric oligothiophene, p-HTIm, that can be utilized for fluorescent imaging of cells. p-HTIm fluorescence in normal cells appeared in a peripheral punctate pattern partially co-localized with lysosomes, whereas a one-sided perinuclear Golgi associated localization of the dye was observed in malignant cells. The uptake of p-HTIm was temperature dependent and the intracellular target was reached within 1 h after staining. The ability of p-HTIm to stain cells was reduced when the imidazole side chain was chemically altered, verifying that specific imidazole side-chain functionalities are necessary for achieving the observed cellular staining. Our findings confirm that properly functionalized oligothiophenes can be utilized as fluorescent tools for vital staining of cells and that the selectivity towards distinct intracellular targets are highly dependent on the side-chain functionalities along the conjugated thiophene backbone.

  • 12.
    Shakeri, Raheleh
    et al.
    University of Tehran, Iran.
    Hosseinkhani, Saman
    Tarbiat Modares University, Iran.
    Los, Marek Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Davoodi, Jamshid
    University of Tehran, Iran.
    Jain, Mayur Vilas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Cieslar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Kaboudanian Ardestani, Sussan
    University of Tehran, Iran.
    Role of the salt bridge between glutamate 546 and arginine 907 in preservation of autoinhibited form of Apaf-12015In: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 81, p. 370-374Article in journal (Refereed)
    Abstract [en]

    Apaf-1, the key element of apoptotic mitochondrial pathway, normally exists in an auto-inhibited form inside the cytosol. WRD-domain of Apaf-1 has a critical role in the preservation of auto-inhibited form; however the underlying mechanism is unclear. It seems the salt bridges between WRD and NOD domains are involved in maintaining the inactive conformation of Apaf-1. At the present study, we have investigated the effect of E546-R907 salt bridge on the maintenance of auto-inhibited form of human Apaf-1. E546 is mutated to glutamine (Q) and arginine (R). Over-expression of wild type Apaf-1 and its E546Q and E546R variants in HEK293T cells does not induce apoptosis unlike - HL-60 cancer cell line. In vitro apoptosome formation assay showed that all variants are cytochrome c and dATP dependent to form apoptosome and activate endogenous procaspase-9 in Apaf-1-knockout MEF cell line. These results suggest that E546 is not a critical residue for preservation of auto-inhibited Apaf-1. Furthermore, the behavior of Apaf-1 variants for in vitro apoptosome formation in HEK293T cell is similar to exogenous wild type Apaf-1. Wild type and its variants can form apoptosome in HEK293T cell with different procaspase-3 processing pattern in the presence and absence of exogenous cytochrome c and dATP. (C) 2015 Elsevier B.V. All rights reserved.

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  • 13.
    Sherrell, Peter
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Cieślar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland.
    Silverå Ejneby, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Sammalisto, Laura
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Gelmi, Amy
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    de Muinck, Ebo
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Brask, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Jan Los, Marek
    Malopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Rational Design of a Conductive Collagen Heart Patch2017In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 17, no 7, article id 1600446Article in journal (Refereed)
    Abstract [en]

    Cardiovascular diseases, including myocardial infarction, are the cause of significant morbidity and mortality globally. Tissue engineering is a key emerging treatment method for supporting and repairing the cardiac scar tissue caused by myocardial infarction. Creating cell supportive scaffolds that can be directly implanted on a myocardial infarct is an attractive solution. Hydrogels made of collagen are highly biocompatible materials that can be molded into a range of shapes suitable for cardiac patch applications. The addition of mechanically reinforcing materials, carbon nanotubes, at subtoxic levels allows for the collagen hydrogels to be strengthened, up to a toughness of 30 J m-1 and a two to threefold improvement in Youngs' modulus, thus improving their viability as cardiac patch materials. The addition of carbon nanotubes is shown to be both nontoxic to stem cells, and when using single-walled carbon nanotubes, supportive of live, beating cardiac cells, providing a pathway for the further development of a cardiac patch.

  • 14.
    Vilas Jain, Mayur
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Jangamreddy, Jaganmohan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Grabarek, Jerzy
    Pomeranian Medical University, Poland.
    Schweizer, Frank
    University of Manitoba, Canada.
    Klonisch, Thomas
    University of Manitoba, Canada.
    Cieslar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Silesian Technical University, Poland.
    Los, Marek Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Pomeranian Medical University, Poland; Medical University of Silesia, Poland.
    Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21(Waf1/Cip1) and p27(kip1)2015In: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 14, no 13, p. 2109-2120Article in journal (Refereed)
    Abstract [en]

    Cancer stem-like cells (CSCs) are a rare subpopulation of cancer cells capable of propagating the disease and causing cancer recurrence. In this study, we found that the cellular localization of PKB/Akt kinase affects the maintenance of CSCs. When Akt tagged with nuclear localization signal (Akt-NLS) was overexpressed in SKBR3 and MDA-MB468 cells, these cells showed a 10-15% increase in the number of cells with CSCs enhanced ALDH activity and demonstrated a CD44(+High)/CD24(-Low) phenotype. This effect was completely reversed in the presence of Akt-specific inhibitor, triciribine. Furthermore, cells overexpressing Akt or Akt-NLS were less likely to be in G0/G1 phase of the cell cycle by inactivating p21(Waf1/Cip1) and exhibited increased clonogenicity and proliferation as assayed by colony-forming assay (mammosphere formation). Thus, our data emphasize the importance the intracellular localization of Akt has on stemness in human breast cancer cells. It also indicates a new robust way for improving the enrichment and culture of CSCs for experimental purposes. Hence, it allows for the development of simpler protocols to study stemness, clonogenic potency, and screening of new chemotherapeutic agents that preferentially target cancer stem cells. Summary: The presented data, (i) shows new, stemness-promoting role of nuclear Akt/PKB kinase, (ii) it underlines the effects of nuclear Akt on cell cycle regulation, and finally (iii) it suggests new ways to study cancer stem-like cells.

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  • 15.
    Wasik, Agata M.
    et al.
    Karolinska Institute, Stockholm, Sweden.
    Grabarek, Jerzy
    Pomeranian Medical University, Szczecin, Poland.
    Pantovic, Aleksandar
    University of Belgrade, Serbia.
    Cieslar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Silesian Technical University, Gliwice, Poland.
    Asgari, Hamid R.
    Tehran University of Medical Sciences, Iran.
    Bundgaard-Nielsen, Caspar
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Aalborg University, Denmark .
    Rafat, Mehrdad
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering.
    Dixon, Ian M.
    University of Manitoba, Winnipeg, Canada.
    Ghavami, Saeid
    University of Manitoba, Winnipeg, Canada.
    Los, Marek Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Pomeranian Medical University, Szczecin, Poland; BioApplications Enterprises, Winnipeg, Canada.
    Reprogramming and Carcinogenesis-Parallels and Distinctions2014In: International Review of Cell and Molecular Biology / [ed] Kwang W Jeon, Elsevier, 2014, Vol. 308, p. 167-203Chapter in book (Refereed)
    Abstract [en]

    Rapid progress made in various areas of regenerative medicine in recent years occurred both at the cellular level, with the Nobel prize-winning discovery of reprogramming (generation of induced pluripotent stem (iPS) cells) and also at the biomaterial level. The use of four transcription factors, Oct3/4, Sox2, c-Myc, and Klf4 (called commonly "Yamanaka factors") for the conversion of differentiated cells, back to the pluripotent/embryonic stage, has opened virtually endless and ethically acceptable source of stem cells for medical use. Various types of stem cells are becoming increasingly popular as starting components for the development of replacement tissues, or artificial organs. Interestingly, many of the transcription factors, key to the maintenance of stemness phenotype in various cells, are also overexpressed in cancer (stem) cells, and some of them may find the use as prognostic factors. In this review, we describe various methods of iPS creation, followed by overview of factors known to interfere with the efficiency of reprogramming. Next, we discuss similarities between cancer stem cells and various stem cell types. Final paragraphs are dedicated to interaction of biomaterials with tissues, various adverse reactions generated as a result of such interactions, and measures available, that allow for mitigation of such negative effects.

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