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  1. Article ; Online: Stimulation with Concanavalin-A Induces IL-17 Production by Canine Peripheral T Cells.

    Ritt, Michelle G / Lindborg, Beth A / O'Brien, Timothy D / Bisignano, Joseph / Modiano, Jaime F

    Veterinary sciences

    2015  Volume 2, Issue 2, Page(s) 43–51

    Abstract: The characteristics of canine IL-17-producing cells are incompletely understood. Expression of mRNA encoding orthologs of IL-17 and the IL-17 receptor has been documented in tissues from dogs with arthritis, inflammatory bowel disease, and lymphoma; ... ...

    Abstract The characteristics of canine IL-17-producing cells are incompletely understood. Expression of mRNA encoding orthologs of IL-17 and the IL-17 receptor has been documented in tissues from dogs with arthritis, inflammatory bowel disease, and lymphoma; however, no associations have been found between IL-17 gene expression and disease phenotype in these conditions. Robust assessment of the role of IL-17-producing cells in dogs will require measuring the frequency of these cells in health and disease in balance with other lymphocyte subsets. The aim of this study was to confirm that the T-cell IL-17 response in dogs is evolutionarily conserved. Canine peripheral blood mononuclear cells were stimulated with Concanavalin A with or without polarizing cytokines. We used a canine specific IL-17 ELISA and flow cytometry to identify IL-17-producing T cells. Accumulation of intracellular IL-17 was observed in stimulated CD4 and CD8 T cells. The addition of pro-inflammatory cytokines appeared to enhance polarization of canine CD4 T cells to the Th17 phenotype. Conversely, the addition of IL-2 in the presence of TGF-β resulted in expansion of Treg cells. We conclude that canine IL-17-producing cells behave similarly to those from humans and mice when stimulated with mitogens and polarized with pro-inflammatory or immune regulatory cytokines.
    Language English
    Publishing date 2015-04-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2768971-2
    ISSN 2306-7381 ; 2306-7381
    ISSN (online) 2306-7381
    ISSN 2306-7381
    DOI 10.3390/vetsci2020043
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A chitosan-hyaluronan-based hydrogel-hydrocolloid supports in vitro culture and differentiation of human mesenchymal stem/stromal cells.

    Lindborg, Beth A / Brekke, John H / Scott, Carolyn M / Chai, Yi Wen / Ulrich, Connor / Sandquist, Lee / Kokkoli, Efrosini / O'Brien, Timothy D

    Tissue engineering. Part A

    2015  Volume 21, Issue 11-12, Page(s) 1952–1962

    Abstract: Three-dimensional (3D) cell culture platforms are increasingly utilized due to their ability to more closely mimic the in vivo microenvironment compared to traditional two-dimensional methods. Limitations of currently available 3D materials include lack ... ...

    Abstract Three-dimensional (3D) cell culture platforms are increasingly utilized due to their ability to more closely mimic the in vivo microenvironment compared to traditional two-dimensional methods. Limitations of currently available 3D materials include lack of cell attachment, long polymerization times, and inclusion of undefined xenobiotics, and cytotoxic cross-linkers. Evaluated here is a unique hydrogel comprised of polyelectrolytic complex (PEC) fibers formed by hyaluronic acid and chitosan (CT). When hydrated with fetal bovine serum containing human mesenchymal stem/stromal cells (hMSCs), a hydrogel with an elastic modulus of 264±38 Pa formed in seconds with cells distributed throughout the matrix. Scanning electron microscopy showed a lattice-like meshwork of PEC fibers forming irregular compartments. hMSCs showed 48% viability during the first 24 h, with cell populations thereafter reaching a steady state for 14 days. hMSCs in the matrix were induced to differentiate to chondrogenic, osteogenic, and adipogenic phenotypes. Emergent features, at days 56 and 70, consisted of chondrogenesis on the surface of hydrogels induced to osteogenic and adipogenic phenotypes. Results indicate that this matrix may be useful for tissue engineering and disease modeling applications.
    MeSH term(s) Adipocytes/cytology ; Bone Marrow Cells/cytology ; Cell Culture Techniques/instrumentation ; Cell Differentiation ; Cellular Microenvironment ; Chitosan ; Chondrocytes/cytology ; Colloids ; Elastic Modulus ; Humans ; Hyaluronic Acid ; Hydrogels ; Materials Testing ; Mesenchymal Stromal Cells/cytology ; Microscopy, Electron, Scanning ; Osteocytes/cytology ; Phenotype ; Rheology ; Tissue Engineering/instrumentation ; Viscosity
    Chemical Substances Colloids ; Hydrogels ; Hyaluronic Acid (9004-61-9) ; Chitosan (9012-76-4)
    Language English
    Publishing date 2015-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2420582-5
    ISSN 1937-335X ; 1937-3341
    ISSN (online) 1937-335X
    ISSN 1937-3341
    DOI 10.1089/ten.TEA.2014.0335
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5500/A: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Stimulation with Concanavalin-A Induces IL-17 Production by Canine Peripheral T Cells

    Michelle G. Ritt / Beth A. Lindborg / Timothy D. O'Brien / Joseph Bisignano / Jaime F. Modiano

    Veterinary Sciences, Vol 2, Iss 2, Pp 43-

    2015  Volume 51

    Abstract: The characteristics of canine IL-17-producing cells are incompletely understood. Expression of mRNA encoding orthologs of IL-17 and the IL-17 receptor has been documented in tissues from dogs with arthritis, inflammatory bowel disease, and lymphoma; ... ...

    Abstract The characteristics of canine IL-17-producing cells are incompletely understood. Expression of mRNA encoding orthologs of IL-17 and the IL-17 receptor has been documented in tissues from dogs with arthritis, inflammatory bowel disease, and lymphoma; however, no associations have been found between IL-17 gene expression and disease phenotype in these conditions. Robust assessment of the role of IL-17-producing cells in dogs will require measuring the frequency of these cells in health and disease in balance with other lymphocyte subsets. The aim of this study was to confirm that the T-cell IL-17 response in dogs is evolutionarily conserved. Canine peripheral blood mononuclear cells were stimulated with Concanavalin A with or without polarizing cytokines. We used a canine specific IL-17 ELISA and flow cytometry to identify IL-17-producing T cells. Accumulation of intracellular IL-17 was observed in stimulated CD4 and CD8 T cells. The addition of pro-inflammatory cytokines appeared to enhance polarization of canine CD4 T cells to the Th17 phenotype. Conversely, the addition of IL-2 in the presence of TGF-β resulted in expansion of Treg cells. We conclude that canine IL-17-producing cells behave similarly to those from humans and mice when stimulated with mitogens and polarized with pro-inflammatory or immune regulatory cytokines.
    Keywords canine ; cytokine ; flow cytometry ; T Lymphocytes ; Veterinary medicine ; SF600-1100
    Subject code 630 ; 610
    Language English
    Publishing date 2015-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Mesenchymal stromal cells inhibit murine syngeneic anti-tumor immune responses by attenuating inflammation and reorganizing the tumor microenvironment.

    Modiano, Jaime F / Lindborg, Beth A / McElmurry, Ron T / Lewellen, Mitzi / Forster, Colleen L / Zamora, Edward A / Schaack, Jerome / Bellgrau, Donald / O'Brien, Timothy D / Tolar, Jakub

    Cancer immunology, immunotherapy : CII

    2015  Volume 64, Issue 11, Page(s) 1449–1460

    Abstract: The potential of mesenchymal stromal cells (MSCs) to inhibit anti-tumor immunity is becoming increasingly well recognized, but the precise steps affected by these cells during the development of an anti-tumor immune response remain incompletely ... ...

    Abstract The potential of mesenchymal stromal cells (MSCs) to inhibit anti-tumor immunity is becoming increasingly well recognized, but the precise steps affected by these cells during the development of an anti-tumor immune response remain incompletely understood. Here, we examined how MSCs affect the steps required to mount an effective anti-tumor immune response following administration of adenovirus Fas ligand (Ad-FasL) in the Lewis lung carcinoma (LL3) model. Administration of bone marrow-derived MSCs with LL3 cells accelerated tumor growth significantly. MSCs inhibited the inflammation induced by Ad-FasL in the primary tumors, precluding their rejection; MSCs also reduced the consequent expansion of tumor-specific T cells in the treated hosts. When immune T cells were transferred to adoptive recipients, MSCs impaired, but did not completely abrogate the ability of these T cells to promote elimination of secondary tumors. This impairment was associated with a modest reduction in tumor-infiltrating T cells, with a significant reduction in tumor-infiltrating macrophages, and with a reorganization of the stromal environment. Our data indicate that MSCs in the tumor environment reduce the efficacy of immunotherapy by creating a functional and anatomic barrier that impairs inflammation, T cell priming and expansion, and T cell function-including recruitment of effector cells.
    MeSH term(s) Adenoviridae/genetics ; Animals ; Carcinoma, Lewis Lung/immunology ; Cytotoxicity, Immunologic ; Fas Ligand Protein/genetics ; Fas Ligand Protein/physiology ; Inflammation/prevention & control ; Mesenchymal Stem Cells/physiology ; Mice ; T-Lymphocytes/immunology ; T-Lymphocytes/physiology ; Tumor Microenvironment
    Chemical Substances Fas Ligand Protein
    Language English
    Publishing date 2015-08-07
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 195342-4
    ISSN 1432-0851 ; 0340-7004
    ISSN (online) 1432-0851
    ISSN 0340-7004
    DOI 10.1007/s00262-015-1749-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1237: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Comparisons of phenotype and immunomodulatory capacity among rhesus bone-marrow-derived mesenchymal stem/stromal cells, multipotent adult progenitor cells, and dermal fibroblasts.

    Sindberg, Gregory M / Lindborg, Beth A / Wang, Qi / Clarkson, Christina / Graham, Melanie / Donahue, Robert / Hering, Bernhard J / Verfaillie, Catherine M / Bansal-Pakala, Pratima / O'Brien, Timothy D

    Journal of medical primatology

    2014  Volume 43, Issue 4, Page(s) 231–241

    Abstract: Background: Potent immunomodulatory effects have been reported for mesenchymal stem/stromal cells (MSCs), multipotent adult progenitor cells (MAPCs), and fibroblasts. However, side-by-side comparisons of these cells specifically regarding ... ...

    Abstract Background: Potent immunomodulatory effects have been reported for mesenchymal stem/stromal cells (MSCs), multipotent adult progenitor cells (MAPCs), and fibroblasts. However, side-by-side comparisons of these cells specifically regarding immunophenotype, gene expression, and suppression of proliferation of CD4(+) and CD8(+) lymphocyte populations have not been reported.
    Methods: We developed MAPC and MSC lines from rhesus macaque bone marrow and fibroblast cell lines from rhesus dermis and assessed phenotypes based upon differentiation potential, flow cytometric analysis of immunophenotype, and quantitative RT-PCR analysis of gene expression. Using allogeneic lymphocyte proliferation assays, we compared the in vitro immunomodulatory potency of each cell type.
    Results and conclusions: Extensive phenotypic similarities exist among each cell type, although immunosuppressive potencies are distinct. MAPCs are most potent, and fibroblasts are the least potent cell type. All three cell types demonstrated immunomodulatory capacity such that each may have potential therapeutic applications such as in organ transplantation, where reduced local immune response is desirable.
    MeSH term(s) Adult Stem Cells/immunology ; Animals ; Bone Marrow Cells/immunology ; Cell Line ; Female ; Fibroblasts/immunology ; Immunosuppression ; Macaca mulatta ; Male ; Mesenchymal Stem Cells/immunology ; Phenotype ; Skin/cytology
    Language English
    Publishing date 2014-05-14
    Publishing country Denmark
    Document type Comparative Study ; Journal Article
    ZDB-ID 121206-0
    ISSN 1600-0684 ; 0047-2565
    ISSN (online) 1600-0684
    ISSN 0047-2565
    DOI 10.1111/jmp.12122
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 819: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article: Rapid Induction of Cerebral Organoids From Human Induced Pluripotent Stem Cells Using a Chemically Defined Hydrogel and Defined Cell Culture Medium.

    Lindborg, Beth A / Brekke, John H / Vegoe, Amanda L / Ulrich, Connor B / Haider, Kerri T / Subramaniam, Sandhya / Venhuizen, Scott L / Eide, Cindy R / Orchard, Paul J / Chen, Weili / Wang, Qi / Pelaez, Francisco / Scott, Carolyn M / Kokkoli, Efrosini / Keirstead, Susan A / Dutton, James R / Tolar, Jakub / O'Brien, Timothy D

    Stem cells translational medicine

    2016  Volume 5, Issue 7, Page(s) 970–979

    Abstract: Unlabelled: Tissue organoids are a promising technology that may accelerate development of the societal and NIH mandate for precision medicine. Here we describe a robust and simple method for generating cerebral organoids (cOrgs) from human pluripotent ... ...

    Abstract Unlabelled: Tissue organoids are a promising technology that may accelerate development of the societal and NIH mandate for precision medicine. Here we describe a robust and simple method for generating cerebral organoids (cOrgs) from human pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. By using no additional neural induction components, cOrgs appeared on the hydrogel surface within 10-14 days, and under static culture conditions, they attained sizes up to 3 mm in greatest dimension by day 28. Histologically, the organoids showed neural rosette and neural tube-like structures and evidence of early corticogenesis. Immunostaining and quantitative reverse-transcription polymerase chain reaction demonstrated protein and gene expression representative of forebrain, midbrain, and hindbrain development. Physiologic studies showed responses to glutamate and depolarization in many cells, consistent with neural behavior. The method of cerebral organoid generation described here facilitates access to this technology, enables scalable applications, and provides a potential pathway to translational applications where defined components are desirable.
    Significance: Tissue organoids are a promising technology with many potential applications, such as pharmaceutical screens and development of in vitro disease models, particularly for human polygenic conditions where animal models are insufficient. This work describes a robust and simple method for generating cerebral organoids from human induced pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. This method, by virtue of its simplicity and use of defined materials, greatly facilitates access to cerebral organoid technology, enables scalable applications, and provides a potential pathway to translational applications where defined components are desirable.
    MeSH term(s) Biomechanical Phenomena ; Brain/cytology ; Brain/metabolism ; Cell Differentiation/genetics ; Cells, Cultured ; Culture Media/chemistry ; Culture Media/pharmacology ; Gene Expression ; Humans ; Hydrogel, Polyethylene Glycol Dimethacrylate/chemistry ; Hydrogel, Polyethylene Glycol Dimethacrylate/pharmacology ; Induced Pluripotent Stem Cells/physiology ; Neurons/cytology ; Neurons/physiology ; Organoids/cytology ; Organoids/physiology ; Tissue Culture Techniques/methods
    Chemical Substances Culture Media ; Hydrogel, Polyethylene Glycol Dimethacrylate (25852-47-5)
    Language English
    Publishing date 2016-05-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2642270-0
    ISSN 2157-6580 ; 2157-6564
    ISSN (online) 2157-6580
    ISSN 2157-6564
    DOI 10.5966/sctm.2015-0305
    Database MEDical Literature Analysis and Retrieval System OnLINE

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