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Artikel ; Online: Human leucocytes processed by fast-rate inertial microfluidics retain conventional functional characteristics.

Carvell, Tom / Burgoyne, Paul / Milne, Laura / Campbell, John D M / Fraser, Alasdair R / Bridle, Helen

2024 Band 21, Heft 212, Seite(n) 20230572

Abstract: The manufacturing of clinical cellular therapies is a complex process frequently requiring manipulation of cells, exchange of buffers and volume reduction. Current manufacturing processes rely on either low throughput open centrifugation-based devices, ... ...

Abstract	The manufacturing of clinical cellular therapies is a complex process frequently requiring manipulation of cells, exchange of buffers and volume reduction. Current manufacturing processes rely on either low throughput open centrifugation-based devices, or expensive closed-process alternatives. Inertial focusing (IF) microfluidic devices offer the potential for high-throughput, inexpensive equipment which can be integrated into a closed system, but to date no IF devices have been approved for use in cell therapy manufacturing, and there is limited evidence for the effects that IF processing has on human cells. The IF device described in this study was designed to simultaneously separate leucocytes, perform buffer exchange and provide a volume reduction to the cell suspension, using high flow rates with high Reynolds numbers. The performance and effects of the IF device were characterized using peripheral blood mononuclear cells and isolated monocytes. Post-processing cell effects were investigated using multi-parameter flow cytometry to track cell viability, functional changes and fate. The IF device was highly efficient at separating CD14+ monocytes (approx. 97% to one outlet, approx. 60% buffer exchange, 15 ml min
Mesh-Begriff(e)	Humans ; Leukocytes, Mononuclear ; Microfluidics ; Leukocytes ; Cell Survival ; Lab-On-A-Chip Devices
Sprache	Englisch
Erscheinungsdatum	2024-03-06
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2156283-0
ISSN	1742-5662 ; 1742-5689
ISSN (online)	1742-5662
ISSN	1742-5689
DOI	10.1098/rsif.2023.0572
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Self-defense against Bacillus anthracis toxins: Is P-selectin the key?

Campbell, John D

Virulence

2017 , Seite(n) 1–3

Sprache	Englisch
Erscheinungsdatum	2017-03-10
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2657572-3
ISSN	2150-5608 ; 2150-5594
ISSN (online)	2150-5608
ISSN	2150-5594
DOI	10.1080/21505594.2017.1304344
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Development of the CpG Adjuvant 1018: A Case Study.

Campbell, John D

Methods in molecular biology (Clifton, N.J.)

2017 Band 1494, Seite(n) 15–27

Abstract: The development of aluminum salts (alum) as vaccine adjuvants was an empirical process with little understanding of the mechanism of action and, with decades of use, it has become clear that there is a need for alternatives where alum-based adjuvants are ...

Abstract	The development of aluminum salts (alum) as vaccine adjuvants was an empirical process with little understanding of the mechanism of action and, with decades of use, it has become clear that there is a need for alternatives where alum-based adjuvants are suboptimal. Oligonucleotides containing unmethylated CpG sequences represent one alternative as they are potent stimulators of the vertebrate innate immune system through activation of Toll-like receptor-9. This chapter outlines the methods used by Dynavax Technologies to progress a CpG-containing oligonucleotide sequence termed 1018 through preclinical and clinical testing as an adjuvant for immunization against hepatitis B virus (HBV). 1018 is a short (22-mer) oligonucleotide sequence containing CpG motifs active in both rodents and primates. Preclinical testing of hepatitis B surface antigen (HBsAg) + 1018 in comparison to HBsAg + alum demonstrated induction of substantially higher antibody titers and a favorable safety profile for 1018. Most importantly, clinical studies with HBsAg vaccination consistently demonstrate more rapid induction of protective antibody titers with 1018 compared to alum in all populations studied, including groups that are harder to immunize such as the elderly and immunocompromised individuals. These studies represent the basis for use of the CpG-motif-containing oligonucleotide 1018 as an improved adjuvant for HBsAg immunogenicity. HBsAg + 1018 (HEPLISAV-B
Sprache	Englisch
Erscheinungsdatum	2017
Erscheinungsland	United States
Dokumenttyp	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-6445-1_2
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: IL-6 and TGF-β-Secreting Adoptively-Transferred Murine Mesenchymal Stromal Cells Accelerate Healing of Psoriasis-like Skin Inflammation and Upregulate IL-17A and TGF-β.

Cuesta-Gomez, Nerea / Medina-Ruiz, Laura / Graham, Gerard J / Campbell, John D M

International journal of molecular sciences

2023 Band 24, Heft 12

Abstract: Mesenchymal stromal cells (MSC) show promise as cellular therapeutics. Psoriasis is a chronic inflammatory disease affecting the skin and the joints. Injury, trauma, infection and medications can trigger psoriasis by disrupting epidermal keratinocyte ... ...

Abstract	Mesenchymal stromal cells (MSC) show promise as cellular therapeutics. Psoriasis is a chronic inflammatory disease affecting the skin and the joints. Injury, trauma, infection and medications can trigger psoriasis by disrupting epidermal keratinocyte proliferation and differentiation, which activates the innate immune system. Pro-inflammatory cytokine secretion drives a T helper 17 response and an imbalance of regulatory T cells. We hypothesized that MSC adoptive cellular therapy could immunomodulate and suppress the effector T cell hyperactivation that underlies the disease. We used the imiquimod-induced psoriasis-like skin inflammation model to study the therapeutic potential of bone marrow and adipose tissue-derived MSC in vivo. We compared the secretome and the in vivo therapeutic potential of MSC with and without cytokine pre-challenge ("licensing"). The infusion of both unlicensed and licensed MSC accelerated the healing of psoriatic lesions, and reduced epidermal thickness and CD3
Mesh-Begriff(e)	Animals ; Mice ; Interleukin-6/metabolism ; Transforming Growth Factor beta/metabolism ; Interleukin-17/metabolism ; Psoriasis/drug therapy ; Skin/metabolism ; Cytokines/metabolism ; Dermatitis/metabolism ; Inflammation/metabolism ; Mesenchymal Stem Cells/metabolism
Chemische Substanzen	Interleukin-6 ; Transforming Growth Factor beta ; Interleukin-17 ; Cytokines
Sprache	Englisch
Erscheinungsdatum	2023-06-14
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241210132
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The use of mesenchymal stromal cells in the treatment of coronavirus disease 2019.

Canham, Maurice A / Campbell, John D M / Mountford, Joanne C

Journal of translational medicine

2020 Band 18, Heft 1, Seite(n) 359

Abstract: More than seven months into the coronavirus disease -19 (COVID-19) pandemic, infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 21.2 million cases and resulted in over 760,000 deaths worldwide so far. As a ... ...

Abstract	More than seven months into the coronavirus disease -19 (COVID-19) pandemic, infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 21.2 million cases and resulted in over 760,000 deaths worldwide so far. As a result, COVID-19 has changed all our lives as we battle to curtail the spread of the infection in the absence of specific therapies against coronaviruses and in anticipation of a proven safe and efficacious vaccine. Common with previous outbreaks of coronavirus infections, SARS and Middle East respiratory syndrome, COVID-19 can lead to acute respiratory distress syndrome (ARDS) that arises due to an imbalanced immune response. While several repurposed antiviral and host-response drugs are under examination as potential treatments, other novel therapeutics are also being explored to alleviate the effects on critically ill patients. The use of mesenchymal stromal cells (MSCs) for COVID-19 has become an attractive avenue down which almost 70 different clinical trial teams have ventured. Successfully trialled for the treatment of other conditions such as multiple sclerosis, osteoarthritis and graft versus host disease, MSCs possess both regenerative and immunomodulatory properties, the latter of which can be harnessed to reduce the severity and longevity of ARDS in patients under intensive care due to SARS-CoV-2 infection.
Mesh-Begriff(e)	Animals ; Betacoronavirus ; Clinical Trials as Topic ; Coronavirus Infections/drug therapy ; Coronavirus Infections/epidemiology ; Coronavirus Infections/immunology ; Coronavirus Infections/therapy ; Humans ; Mesenchymal Stem Cell Transplantation ; Pandemics ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/immunology ; Pneumonia, Viral/therapy ; Respiratory Distress Syndrome, Adult/etiology ; Respiratory Distress Syndrome, Adult/immunology ; Respiratory Distress Syndrome, Adult/therapy ; Translational Medical Research
Schlagwörter	covid19
Sprache	Englisch
Erscheinungsdatum	2020-09-21
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1479-5876
ISSN (online)	1479-5876
DOI	10.1186/s12967-020-02532-4
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Chemokines and their receptors: predictors of the therapeutic potential of mesenchymal stromal cells.

Cuesta-Gomez, Nerea / Graham, Gerard J / Campbell, John D M

Journal of translational medicine

2021 Band 19, Heft 1, Seite(n) 156

Abstract: Multipotent mesenchymal stromal cells (MSCs) are promising cellular therapeutics for the treatment of inflammatory and degenerative disorders due to their anti-inflammatory, immunomodulatory and regenerative potentials. MSCs can be sourced from a variety ...

Abstract	Multipotent mesenchymal stromal cells (MSCs) are promising cellular therapeutics for the treatment of inflammatory and degenerative disorders due to their anti-inflammatory, immunomodulatory and regenerative potentials. MSCs can be sourced from a variety of tissues within the body, but bone marrow is the most frequently used starting material for clinical use. The chemokine family contains many regulators of inflammation, cellular function and cellular migration-all critical factors in understanding the potential potency of a novel cellular therapeutic. In this review, we focus on expression of chemokine receptors and chemokine ligands by MSCs isolated from different tissues. We discuss the differential migratory, angiogenetic and immunomodulatory potential to understand the role that tissue source of MSC may play within a clinical context. Furthermore, this is strongly associated with leukocyte recruitment, immunomodulatory potential and T cell inhibition potential and we hypothesize that chemokine profiling can be used to predict the in vivo therapeutic potential of MSCs isolated from new sources and compare them to BM MSCs.
Mesh-Begriff(e)	Bone Marrow Cells ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Chemokines ; Humans ; Immunomodulation ; Mesenchymal Stem Cells ; Receptors, Chemokine
Chemische Substanzen	Chemokines ; Receptors, Chemokine
Sprache	Englisch
Erscheinungsdatum	2021-04-17
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-021-02822-5
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: A CpG 1018 adjuvanted neuraminidase vaccine provides robust protection from influenza virus challenge in mice.

Strohmeier, Shirin / Amanat, Fatima / Campbell, John D / Traquina, Paula / Coffman, Robert L / Krammer, Florian

NPJ vaccines

2022 Band 7, Heft 1, Seite(n) 81

Abstract: Influenza virus infections pose a significant threat to global health. Vaccination is the main countermeasure against influenza virus spread, however, the effectiveness of vaccines is variable. Current seasonal influenza virus vaccines mostly rely on the ...

Abstract	Influenza virus infections pose a significant threat to global health. Vaccination is the main countermeasure against influenza virus spread, however, the effectiveness of vaccines is variable. Current seasonal influenza virus vaccines mostly rely on the immunodominant hemagglutinin (HA) glycoprotein on the viral surface, which usually leads to a narrow and strain-specific immune response. The HA undergoes constant antigenic drift, which can lead to a dramatic loss in vaccine effectiveness, requiring the annual reformulation and readministration of influenza virus vaccines. Recently, it has been demonstrated that the subdominant glycoprotein, neuraminidase (NA), is an attractive target for vaccine development. Here, we tested a newly developed recombinant influenza virus N1 neuraminidase vaccine candidate, named N1-MPP, adjuvanted with CpG 1018, a TLR9 agonist. Additionally, N2-MPP and B-NA-MPP vaccine constructs have been generated to cover the range of influenza viruses that are seasonally circulating in humans. These constructs have been characterized in vitro and in vivo regarding their functionality and protective potential. Furthermore, a trivalent NA-MPP mix was tested. No antigenic competition between the individual NA constructs was detected. By adjuvating the recombinant protein constructs with CpG 1018 it was possible to induce a strong and robust immune response against the NA, which provided full protection against morbidity and mortality after high lethal challenges in vivo. This study provides important insights for the development of a broadly protective NA-based influenza virus vaccine candidate.
Sprache	Englisch
Erscheinungsdatum	2022-07-22
Erscheinungsland	England
Dokumenttyp	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-022-00486-w
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Development of Good Manufacturing Practice-Compatible Isolation and Culture Methods for Human Olfactory Mucosa-Derived Mesenchymal Stromal Cells.

Kelly, Christopher J / Lindsay, Susan L / Smith, Rebecca Sherrard / Keh, Siew / Cunningham, Kyle T / Thümmler, Katja / Maizels, Rick M / Campbell, John D M / Barnett, Susan C

International journal of molecular sciences

2024 Band 25, Heft 2

Abstract: Demyelination in the central nervous system (CNS) resulting from injury or disease can cause loss of nerve function and paralysis. Cell therapies intended to promote remyelination of axons are a promising avenue of treatment, with mesenchymal stromal ... ...

Abstract	Demyelination in the central nervous system (CNS) resulting from injury or disease can cause loss of nerve function and paralysis. Cell therapies intended to promote remyelination of axons are a promising avenue of treatment, with mesenchymal stromal cells (MSCs) a prominent candidate. We have previously demonstrated that MSCs derived from human olfactory mucosa (hOM-MSCs) promote myelination to a greater extent than bone marrow-derived MSCs (hBM-MSCs). However, hOM-MSCs were developed using methods and materials that were not good manufacturing practice (GMP)-compliant. Before considering these cells for clinical use, it is necessary to develop a method for their isolation and expansion that is readily adaptable to a GMP-compliant environment. We demonstrate here that hOM-MSCs can be derived without enzymatic tissue digestion or cell sorting and without culture antibiotics. They grow readily in GMP-compliant media and express typical MSC surface markers. They robustly produce CXCL12 (a key secretory factor in promoting myelination) and are pro-myelinating in in vitro rodent CNS cultures. GMP-compliant hOM-MSCs are comparable in this respect to those grown in non-GMP conditions. However, when assessed in an in vivo model of demyelinating disease (experimental autoimmune encephalitis, EAE), they do not significantly improve disease scores compared with controls, indicating further pre-clinical evaluation is necessary before their advancement to clinical trials.
Mesh-Begriff(e)	Humans ; Culture Techniques ; Anti-Bacterial Agents ; Axons ; Biological Transport ; Mesenchymal Stem Cells
Chemische Substanzen	Anti-Bacterial Agents
Sprache	Englisch
Erscheinungsdatum	2024-01-06
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25020743
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The use of mesenchymal stromal cells in the treatment of coronavirus disease 2019

Canham, Maurice A. / Campbell, John D. M. / Mountford, Joanne C.

Journal of Translational Medicine

2020 Band 18, Heft 1

Abstract: Abstract More than seven months into the coronavirus disease -19 (COVID-19) pandemic, infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 21.2 million cases and resulted in over 760,000 deaths worldwide so far. ...

Abstract	Abstract More than seven months into the coronavirus disease -19 (COVID-19) pandemic, infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 21.2 million cases and resulted in over 760,000 deaths worldwide so far. As a result, COVID-19 has changed all our lives as we battle to curtail the spread of the infection in the absence of specific therapies against coronaviruses and in anticipation of a proven safe and efficacious vaccine. Common with previous outbreaks of coronavirus infections, SARS and Middle East respiratory syndrome, COVID-19 can lead to acute respiratory distress syndrome (ARDS) that arises due to an imbalanced immune response. While several repurposed antiviral and host-response drugs are under examination as potential treatments, other novel therapeutics are also being explored to alleviate the effects on critically ill patients. The use of mesenchymal stromal cells (MSCs) for COVID-19 has become an attractive avenue down which almost 70 different clinical trial teams have ventured. Successfully trialled for the treatment of other conditions such as multiple sclerosis, osteoarthritis and graft versus host disease, MSCs possess both regenerative and immunomodulatory properties, the latter of which can be harnessed to reduce the severity and longevity of ARDS in patients under intensive care due to SARS-CoV-2 infection.
Schlagwörter	General Biochemistry, Genetics and Molecular Biology ; General Medicine ; covid19
Sprache	Englisch
Verlag	Springer Science and Business Media LLC
Erscheinungsland	us
Dokumenttyp	Artikel ; Online
ISSN	1479-5876
DOI	10.1186/s12967-020-02532-4
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel: The use of mesenchymal stromal cells in the treatment of coronavirus disease 2019

Canham, Maurice A / Campbell, John D M / Mountford, Joanne C

J Transl Med

Abstract	More than seven months into the coronavirus disease -19 (COVID-19) pandemic, infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 21.2 million cases and resulted in over 760,000 deaths worldwide so far. As a result, COVID-19 has changed all our lives as we battle to curtail the spread of the infection in the absence of specific therapies against coronaviruses and in anticipation of a proven safe and efficacious vaccine. Common with previous outbreaks of coronavirus infections, SARS and Middle East respiratory syndrome, COVID-19 can lead to acute respiratory distress syndrome (ARDS) that arises due to an imbalanced immune response. While several repurposed antiviral and host-response drugs are under examination as potential treatments, other novel therapeutics are also being explored to alleviate the effects on critically ill patients. The use of mesenchymal stromal cells (MSCs) for COVID-19 has become an attractive avenue down which almost 70 different clinical trial teams have ventured. Successfully trialled for the treatment of other conditions such as multiple sclerosis, osteoarthritis and graft versus host disease, MSCs possess both regenerative and immunomodulatory properties, the latter of which can be harnessed to reduce the severity and longevity of ARDS in patients under intensive care due to SARS-CoV-2 infection.
Schlagwörter	covid19
Verlag	WHO
Dokumenttyp	Artikel
Anmerkung	WHO #Covidence: #781480
Datenquelle	COVID19

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