LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 3 of total 3

Search options

  1. Article ; Online: Dose and duration of interferon γ pre-licensing interact with donor characteristics to influence the expression and function of indoleamine-2,3-dioxygenase in mesenchymal stromal cells.

    Boyt, Devlin T / Boland, Lauren K / Burand, Anthony J / Brown, Alex J / Ankrum, James A

    Journal of the Royal Society, Interface

    2020  Volume 17, Issue 167, Page(s) 20190815

    Abstract: Human mesenchymal stromal cells (MSCs) are a leading cell therapy candidate for the treatment of immune and inflammatory diseases due to their potent regulation of immune cells. MSC expression of indoleamine-2,3-dioxygenase (IDO) upon interferon γ (IFNγ) ...

    Abstract Human mesenchymal stromal cells (MSCs) are a leading cell therapy candidate for the treatment of immune and inflammatory diseases due to their potent regulation of immune cells. MSC expression of indoleamine-2,3-dioxygenase (IDO) upon interferon γ (IFNγ) exposure has been proposed as both a sentinel marker and key mediator of MSC immunomodulatory potency. Rather than wait for
    MeSH term(s) Cell Proliferation ; Cells, Cultured ; Humans ; Immunomodulation ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Interferon-gamma ; Leukocytes, Mononuclear ; Mesenchymal Stem Cells
    Chemical Substances Indoleamine-Pyrrole 2,3,-Dioxygenase ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2020-06-17
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; 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.2019.0815
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells.

    Burand, Anthony J / Di, Lin / Boland, Lauren K / Boyt, Devlin T / Schrodt, Michael V / Santillan, Donna A / Ankrum, James A

    Frontiers in immunology

    2020  Volume 11, Page(s) 143

    Abstract: Mesenchymal stromal cells (MSCs) are administered locally to treat sites of inflammation. Local delivery is known to cause MSCs to aggregate into "spheroids," which alters gene expression and phenotype. While adherent MSCs are highly efficient in their ... ...

    Abstract Mesenchymal stromal cells (MSCs) are administered locally to treat sites of inflammation. Local delivery is known to cause MSCs to aggregate into "spheroids," which alters gene expression and phenotype. While adherent MSCs are highly efficient in their inhibition of T cells, whether or not this property is altered upon MSC aggregation has not been thoroughly determined. In this study, we discovered that aggregation of MSCs into spheroids causes them to lose their T cell-suppressive abilities. Interestingly, adding budesonide, a topical glucocorticoid steroid, alongside spheroids partially restored MSC suppression of T cell proliferation. Through a series of inhibition and add-back studies, we determined budesonide acts synergistically with spheroid MSC-produced PGE2 to suppress T cell proliferation through the PGE2 receptors EP2 and EP4. These findings highlight critical differences between adherent and spheroid MSC interactions with human immune cells that have significant translational consequences. In addition, we uncovered a mechanism through which spheroid MSC suppression of T cells can be partly restored. By understanding the phenotypic changes that occur upon MSC aggregation and the impact of MSC drug interactions, improved immunosuppressive MSC therapies for localized delivery can be designed.
    MeSH term(s) Bone Marrow Cells/metabolism ; Budesonide/pharmacology ; Cell Aggregation ; Cell Proliferation/drug effects ; Cells, Cultured ; Coculture Techniques ; Dinoprostone/metabolism ; Dinoprostone/pharmacology ; Humans ; Immunologic Factors/metabolism ; Immunomodulation/immunology ; Lymphocyte Activation ; Mesenchymal Stem Cells/immunology ; Mesenchymal Stem Cells/metabolism ; Signal Transduction/drug effects ; Spheroids, Cellular/immunology ; Spheroids, Cellular/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Tissue Donors ; Umbilical Cord/cytology
    Chemical Substances Immunologic Factors ; Budesonide (51333-22-3) ; Dinoprostone (K7Q1JQR04M)
    Language English
    Publishing date 2020-02-25
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.00143
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Nature vs. Nurture: Defining the Effects of Mesenchymal Stromal Cell Isolation and Culture Conditions on Resiliency to Palmitate Challenge.

    Boland, Lauren K / Burand, Anthony J / Boyt, Devlin T / Dobroski, Hannah / Di, Lin / Liszewski, Jesse N / Schrodt, Michael V / Frazer, Maria K / Santillan, Donna A / Ankrum, James A

    Frontiers in immunology

    2019  Volume 10, Page(s) 1080

    Abstract: As MSC products move from early development to clinical translation, culture conditions shift from xeno- to xeno-free systems. However, the impact of isolation and culture-expansion methods on the long-term resiliency of MSCs within challenging ... ...

    Abstract As MSC products move from early development to clinical translation, culture conditions shift from xeno- to xeno-free systems. However, the impact of isolation and culture-expansion methods on the long-term resiliency of MSCs within challenging transplant environments is not fully understood. Recent work in our lab has shown that palmitate, a saturated fatty acid elevated in the serum of patients with obesity, causes MSCs to convert from an immunosuppressive to an immunostimulatory state at moderate to high physiological levels. This demonstrated that metabolically-diseased environments, like obesity, alter the immunomodulatory efficacy of healthy donor MSCs. In addition, it highlighted the need to test MSC efficacy not only in ideal conditions, but within challenging metabolic environments. To determine how the choice of xeno- vs. xeno-free media during isolation and expansion would affect future immunosuppressive function, umbilical cord explants from seven donors were subdivided and cultured within xeno- (fetal bovine serum, FBS) or xeno-free (human platelet lysate, PLT) medias, creating 14 distinct MSC preparations. After isolation and primary expansion, umbilical cord MSCs (ucMSC) were evaluated according to the ISCT minimal criteria for MSCs. Following baseline characterization, ucMSC were exposed to physiological doses of palmitate and analyzed for metabolic health, apoptotic induction, and immunomodulatory potency in co-cultures with stimulated human peripheral blood mononuclear cells. The paired experimental design (each ucMSC donor grown in two distinct culture environments) allowed us to delineate the contribution of inherent (nature) vs. environmentally-driven (nurture) donor characteristics to the phenotypic response of ucMSC during palmitate exposure. Culturing MSCs in PLT-media led to more consistent growth characteristics during the isolation and expansion for all donors, resulting in faster doubling times and higher cell yields compared to FBS. Upon palmitate challenge, PLT-ucMSCs showed a higher susceptibility to palmitate-induced metabolic disturbance, but less susceptibility to palmitate-induced apoptosis. Most striking however, was that the PLT-ucMSCs resisted the conversion to an immunostimulatory phenotype better than their FBS counterparts. Interestingly, examining MSC suppression of PBMC proliferation at physiologic doses of palmitate magnified the differences between donors, highlighting the utility of evaluating MSC products in stress-based assays that reflect the challenges MSCs may encounter post-transplantation.
    MeSH term(s) Blood Platelets/cytology ; Cell Culture Techniques ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Cells, Cultured ; Culture Media/pharmacology ; Humans ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/immunology ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology ; Obesity/blood ; Obesity/pathology ; Palmitates/blood ; Palmitates/metabolism ; Umbilical Cord/cytology
    Chemical Substances Culture Media ; Palmitates
    Language English
    Publishing date 2019-05-10
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2019.01080
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top