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  1. Article ; Online: In the eye of the COVID-19 cytokine storm.

    Vaninov, Natalie

    Nature reviews. Immunology

    2020  Volume 20, Issue 5, Page(s) 277

    Keywords covid19
    Language English
    Publishing date 2020-04-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/s41577-020-0305-6
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  3. Article ; Online: In the eye of the COVID-19 cytokine storm

    Vaninov, Natalie

    Nature Reviews Immunology

    2020  Volume 20, Issue 5, Page(s) 277–277

    Keywords Immunology ; covid19
    Language English
    Publisher Springer Science and Business Media LLC
    Publishing country us
    Document type Article ; Online
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/s41577-020-0305-6
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  4. Article ; Online: An immunogenetic basis for lung cancer risk.

    Krishna, Chirag / Tervi, Anniina / Saffern, Miriam / Wilson, Eric A / Yoo, Seong-Keun / Mars, Nina / Roudko, Vladimir / Cho, Byuri Angela / Jones, Samuel Edward / Vaninov, Natalie / Selvan, Myvizhi Esai / Gümüş, Zeynep H / Lenz, Tobias L / Merad, Miriam / Boffetta, Paolo / Martínez-Jiménez, Francisco / Ollila, Hanna M / Samstein, Robert M / Chowell, Diego

    Science (New York, N.Y.)

    2024  Volume 383, Issue 6685, Page(s) eadi3808

    Abstract: Cancer risk is influenced by inherited mutations, DNA replication errors, and environmental factors. However, the influence of genetic variation in immunosurveillance on cancer risk is not well understood. Leveraging population-level data from the UK ... ...

    Abstract Cancer risk is influenced by inherited mutations, DNA replication errors, and environmental factors. However, the influence of genetic variation in immunosurveillance on cancer risk is not well understood. Leveraging population-level data from the UK Biobank and FinnGen, we show that heterozygosity at the
    MeSH term(s) Humans ; Histocompatibility Antigens Class II/genetics ; Lung Neoplasms/genetics ; Lung Neoplasms/immunology ; Macrophages, Alveolar/immunology ; Risk Factors ; Loss of Heterozygosity ; Smoking/immunology ; Immunologic Surveillance/genetics ; Middle Aged ; Aged ; Aged, 80 and over ; Genetic Predisposition to Disease ; Chromosome Mapping ; Polymorphism, Single Nucleotide
    Chemical Substances Histocompatibility Antigens Class II
    Language English
    Publishing date 2024-02-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.adi3808
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  5. Article ; Online: Convergence of Cell Pharmacology and Drug Delivery.

    Aijaz, Ayesha / Vaninov, Natalie / Allen, Ashley / Barcia, Rita N / Parekkadan, Biju

    Stem cells translational medicine

    2019  Volume 8, Issue 9, Page(s) 874–879

    Abstract: Cellular therapy is enabling new approaches to tackle significant unmet needs in areas such as regenerative medicine and immunotherapy. The pharmacology of cell therapeutics becomes of critical importance to assure that these new drugs work reproducibly ... ...

    Abstract Cellular therapy is enabling new approaches to tackle significant unmet needs in areas such as regenerative medicine and immunotherapy. The pharmacology of cell therapeutics becomes of critical importance to assure that these new drugs work reproducibly and effectively. Cell pharmacology can benefit from adapting principles of classical molecular drug pharmacokinetics (PK) and pharmacodynamics (PD) to quantitatively understand rate-limiting constraints of cell fate after administration. Future innovations focused on improvements in drug delivery using a PK/PD perspective can aid in designing a cell therapeutic product to overcome any pharmacological barriers for a given disease application. Herein, we present a perspective on the development of an ex vivo mesenchymal stromal therapeutic using a PK/PD framework and also present examples of general cell engineering techniques that implicitly influence the PK/PD curve by genetically modifying cells to regulate their in vivo duration, biodistribution, and activity. Stem Cells Translational Medicine 2019;8:874&879.
    MeSH term(s) Drug Delivery Systems ; Half-Life ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Metabolic Engineering ; Receptors, Antigen, T-Cell/metabolism ; Regenerative Medicine
    Chemical Substances Receptors, Antigen, T-Cell
    Language English
    Publishing date 2019-05-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2642270-0
    ISSN 2157-6580 ; 2157-6580
    ISSN (online) 2157-6580
    ISSN 2157-6580
    DOI 10.1002/sctm.19-0019
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  6. Article ; Online: Convergence of Cell Pharmacology and Drug Delivery

    Ayesha Aijaz / Natalie Vaninov / Ashley Allen / Rita N. Barcia / Biju Parekkadan

    Stem Cells Translational Medicine, Vol 8, Iss 9, Pp 874-

    2019  Volume 879

    Abstract: Summary Cellular therapy is enabling new approaches to tackle significant unmet needs in areas such as regenerative medicine and immunotherapy. The pharmacology of cell therapeutics becomes of critical importance to assure that these new drugs work ... ...

    Abstract Summary Cellular therapy is enabling new approaches to tackle significant unmet needs in areas such as regenerative medicine and immunotherapy. The pharmacology of cell therapeutics becomes of critical importance to assure that these new drugs work reproducibly and effectively. Cell pharmacology can benefit from adapting principles of classical molecular drug pharmacokinetics (PK) and pharmacodynamics (PD) to quantitatively understand rate‐limiting constraints of cell fate after administration. Future innovations focused on improvements in drug delivery using a PK/PD perspective can aid in designing a cell therapeutic product to overcome any pharmacological barriers for a given disease application. Herein, we present a perspective on the development of an ex vivo mesenchymal stromal therapeutic using a PK/PD framework and also present examples of general cell engineering techniques that implicitly influence the PK/PD curve by genetically modifying cells to regulate their in vivo duration, biodistribution, and activity. Stem Cells Translational Medicine 2019;8:874&879
    Keywords Medicine (General) ; R5-920 ; Cytology ; QH573-671
    Subject code 610
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher Oxford University Press
    Document type Article ; Online
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  7. Article ; Online: Author Correction: Mesenchymal Stromal Cell Bioreactor for Ex Vivo Reprogramming of Human Immune Cells.

    Allen, Ashley / Vaninov, Natalie / Li, Matthew / Nguyen, Sunny / Singh, Maneet / Igo, Peter / Tilles, Arno W / O'Rourke, Brian / Miller, Brian L K / Parekkadan, Biju / Barcia, Rita N

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 15451

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Language English
    Publishing date 2020-09-17
    Publishing country England
    Document type Journal Article ; Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-72947-y
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  8. Article ; Online: Mesenchymal Stromal Cell Bioreactor for Ex Vivo Reprogramming of Human Immune Cells.

    Allen, Ashley / Vaninov, Natalie / Li, Matthew / Nguyen, Sunny / Singh, Maneet / Igo, Peter / Tilles, Arno W / O'Rourke, Brian / Miller, Brian L K / Parekkadan, Biju / Barcia, Rita N

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 10142

    Abstract: Bone marrow mesenchymal stromal cells (MSCs) have been studied for decades as potent immunomodulators. Clinically, they have shown some promise but with limited success. Here, we report the ability of a scalable hollow fiber bioreactor to effectively ... ...

    Abstract Bone marrow mesenchymal stromal cells (MSCs) have been studied for decades as potent immunomodulators. Clinically, they have shown some promise but with limited success. Here, we report the ability of a scalable hollow fiber bioreactor to effectively maintain ideal MSC function as a single population while also being able to impart an immunoregulatory effect when cultured in tandem with an inflamed lymphocyte population. MSCs were seeded on the extraluminal side of hollow fibers within a bioreactor where they indirectly interact with immune cells flowing within the lumen of the fibers. MSCs showed a stable and predictable metabolite and secreted factor profile during several days of perfusion culture. Exposure of bioreactor-seeded MSCs to inflammatory stimuli reproducibly switched MSC secreted factor profiles and altered microvesicle composition. Furthermore, circulating, activated human peripheral blood mononuclear cells (PBMCs) were suppressed by MSC bioreactor culture confirmed by a durable change in their immunophenotype and function. This platform was useful to study a model of immobilized MSCs and circulating immune cells and showed that monocytes play an important role in MSC driven immunomodulation. This coculture technology can have broad implications for use in studying MSC-immune interactions under flow conditions as well as in the generation of ex vivo derived immune cellular therapeutics.
    MeSH term(s) Bioreactors ; Bone Marrow Cells ; Cell Culture Techniques/methods ; Cells, Cultured ; Cellular Reprogramming ; Cellular Reprogramming Techniques/methods ; Humans ; Immunomodulation/immunology ; Leukocytes, Mononuclear/immunology ; Lymphocytes/immunology ; Mesenchymal Stem Cells/immunology
    Language English
    Publishing date 2020-06-23
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-67039-w
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  9. Article ; Online: Pharmacological effects of ex vivo mesenchymal stem cell immunotherapy in patients with acute kidney injury and underlying systemic inflammation.

    Swaminathan, Madhav / Kopyt, Nelson / Atta, Mohamed G / Radhakrishnan, Jai / Umanath, Kausik / Nguyen, Sunny / O'Rourke, Brian / Allen, Ashley / Vaninov, Natalie / Tilles, Arno / LaPointe, Elizabeth / Blair, Andrew / Gemmiti, Chris / Miller, Brian / Parekkadan, Biju / Barcia, Rita N

    Stem cells translational medicine

    2021  Volume 10, Issue 12, Page(s) 1588–1601

    Abstract: Mesenchymal stem cells (MSCs) have natural immunoregulatory functions that have been explored for medicinal use as a cell therapy with limited success. A phase Ib study was conducted to evaluate the safety and immunoregulatory mechanism of action of MSCs ...

    Abstract Mesenchymal stem cells (MSCs) have natural immunoregulatory functions that have been explored for medicinal use as a cell therapy with limited success. A phase Ib study was conducted to evaluate the safety and immunoregulatory mechanism of action of MSCs using a novel ex vivo product (SBI-101) to preserve cell activity in patients with severe acute kidney injury. Pharmacological data demonstrated MSC-secreted factor activity that was associated with anti-inflammatory signatures in the molecular and cellular profiling of patient blood. Systems biology analysis captured multicompartment effects consistent with immune reprogramming and kidney tissue repair. Although the study was not powered for clinical efficacy, these results are supportive of the therapeutic hypothesis, namely, that treatment with SBI-101 elicits an immunotherapeutic response that triggers an accelerated phenotypic switch from tissue injury to tissue repair. Ex vivo administration of MSCs, with increased power of testing, is a potential new biological delivery paradigm that assures sustained MSC activity and immunomodulation.
    MeSH term(s) Acute Kidney Injury/therapy ; Humans ; Immunomodulation ; Immunotherapy ; Inflammation/therapy ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells
    Language English
    Publishing date 2021-09-28
    Publishing country England
    Document type Clinical Trial, Phase I ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2642270-0
    ISSN 2157-6580 ; 2157-6580
    ISSN (online) 2157-6580
    ISSN 2157-6580
    DOI 10.1002/sctm.21-0043
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  10. Article ; Online: Mesenchymal Stromal Cell Bioreactor for Ex Vivo Reprogramming of Human Immune Cells

    Ashley Allen / Natalie Vaninov / Matthew Li / Sunny Nguyen / Peter Igo / Arno W. Tilles / Brian O’Rourke / Brian L. K. Miller / Biju Parekkadan / Rita N. Barcia

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 13

    Abstract: Abstract Bone marrow mesenchymal stromal cells (MSCs) have been studied for decades as potent immunomodulators. Clinically, they have shown some promise but with limited success. Here, we report the ability of a scalable hollow fiber bioreactor to ... ...

    Abstract Abstract Bone marrow mesenchymal stromal cells (MSCs) have been studied for decades as potent immunomodulators. Clinically, they have shown some promise but with limited success. Here, we report the ability of a scalable hollow fiber bioreactor to effectively maintain ideal MSC function as a single population while also being able to impart an immunoregulatory effect when cultured in tandem with an inflamed lymphocyte population. MSCs were seeded on the extraluminal side of hollow fibers within a bioreactor where they indirectly interact with immune cells flowing within the lumen of the fibers. MSCs showed a stable and predictable metabolite and secreted factor profile during several days of perfusion culture. Exposure of bioreactor-seeded MSCs to inflammatory stimuli reproducibly switched MSC secreted factor profiles and altered microvesicle composition. Furthermore, circulating, activated human peripheral blood mononuclear cells (PBMCs) were suppressed by MSC bioreactor culture confirmed by a durable change in their immunophenotype and function. This platform was useful to study a model of immobilized MSCs and circulating immune cells and showed that monocytes play an important role in MSC driven immunomodulation. This coculture technology can have broad implications for use in studying MSC-immune interactions under flow conditions as well as in the generation of ex vivo derived immune cellular therapeutics.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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