scholarly journals Modulation of the Early Inflammatory Microenvironment in the Alkali-Burned Eye by Systemically Administered Interferon-γ-Treated Mesenchymal Stromal Cells

2014 ◽  
Vol 23 (20) ◽  
pp. 2490-2500 ◽  
Author(s):  
Eliska Javorkova ◽  
Peter Trosan ◽  
Alena Zajicova ◽  
Magdalena Krulova ◽  
Michaela Hajkova ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Interferon Γ ◽  
Inflammatory Microenvironment

scholarly journals Cryopreserved mesenchymal stromal cells display impaired immunosuppressive properties as a result of heat-shock response and impaired interferon-γ licensing

Cytotherapy ◽  
2012 ◽  
Vol 14 (2) ◽  
pp. 147-152 ◽  
Author(s):  
Moïra François ◽  
Ian B. Copland ◽  
Shala Yuan ◽  
Raphaëlle Romieu-Mourez ◽  
Edmund K. Waller ◽  
...  
Keyword(s):  
Heat Shock ◽  
Mesenchymal Stromal Cells ◽  
Heat Shock Response ◽  
Stromal Cells ◽  
Interferon Γ ◽  
Shock Response

scholarly journals Immunomodulatory effects of interferon-γ on human fetal cardiac mesenchymal stromal cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Karl-Henrik Grinnemo ◽  
Marie Löfling ◽  
Lubov Nathanson ◽  
Roland Baumgartner ◽  
Daniel F. J. Ketelhuth ◽  
...  
Keyword(s):  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
T Cell Activation ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
First Trimester ◽  
Interferon Γ ◽  
Systematic Evaluation ◽  
Immunomodulatory Effects ◽  
Functional Changes

Abstract Background Mesenchymal stromal cells (MSCs), due to their regenerative and immunomodulatory properties, are therapeutically used for diseases, including heart failure. As early gestational-phase embryonic tissues exhibit extraordinary regenerative potential, fetal MSCs exposed to inflammation offer a unique opportunity to evaluate molecular mechanisms underlying preferential healing, and investigate their inherent abilities to communicate with the immune system during development. The principal aim of this study was to evaluate the effects of interferon-γ (IFNγ) on the immunomodulatory effects of first-trimester human fetal cardiac (hfc)-MSCs. Methods hfcMSCs (gestational week 8) were exposed to IFNγ, with subsequent analysis of the whole transcriptome, based on RNA sequencing. Exploration of surface-expressed immunoregulatory mediators and modulation of T cell responses were performed by flow cytometry. Presence and activity of soluble mediators were assessed by ELISA or high-performance liquid chromatography. Results Stimulation of hfcMSCs with IFNγ revealed significant transcriptional changes, particularly in respect to the expression of genes belonging to antigen presentation pathways, cell cycle control, and interferon signaling. Expression of immunomodulatory genes and associated functional changes, including indoleamine 2,3-dioxygenase activity, and regulation of T cell activation and proliferation via programmed cell death protein (PD)-1 and its ligands PD-L1 and PD-L2, were significantly upregulated. These immunoregulatory molecules diminished rapidly upon withdrawal of inflammatory stimulus, indicating a high degree of plasticity by hfcMSCs. Conclusions To our knowledge, this is the first study performing a systematic evaluation of inflammatory responses and immunoregulatory properties of first-trimester cardiac tissue. In summary, our study demonstrates the dynamic responsiveness of hfcMSCs to inflammatory stimuli. Further understanding as to the immunoregulatory properties of hfcMSCs may be of benefit in the development of novel stromal cell therapeutics for cardiovascular disease.

scholarly journals 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

2020 ◽  
Vol 17 (167) ◽  
pp. 20190815
Author(s):  
Devlin T. Boyt ◽  
Lauren K. Boland ◽  
Anthony J. Burand ◽  
Alex J. Brown ◽  
James A. Ankrum
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Interferon Γ ◽  
Relative Role ◽  
Peripheral Blood Mononuclear ◽  
High Performing ◽  
Indoleamine 2,3 Dioxygenase

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 in vivo exposure to cytokines, MSCs can be pre-licensed during manufacturing to enhance IDO expression. In this study, we systematically examine the relative role that the dose of IFNγ, the duration of pre-licensing and the donor of origin play in dictating MSC production of functional IDO. We find that across three human MSC donors, MSCs increase their expression of IDO in response to both increased dose of IFNγ and duration of pre-licensing. However, with extended pre-licensing, the expression of IDO no longer predicts MSCs ability to suppress activated peripheral blood mononuclear cells. In addition, pre-licensing dose and duration are revealed to be minor modifiers of MSCs inherent potency, and thus cannot be manipulated to boost poor donors to the levels of high-performing donors. Thus, the dose and duration of pre-licensing should be tailored to optimize performance of specific donors and an emphasis on donor selection is needed to realize significant benefits of pre-licensing.

scholarly journals Morphological profiling using machine learning reveals emergent subpopulations of interferon-γ–stimulated mesenchymal stromal cells that predict immunosuppression

Cytotherapy ◽  
2019 ◽  
Vol 21 (1) ◽  
pp. 17-31 ◽  
Author(s):  
ROSS A. MARKLEIN ◽  
MATTHEW W. KLINKER ◽  
KATHERINE A. DRAKE ◽  
HANNAH G. POLIKOWSKY ◽  
ELIZABETH C. LESSEY-MORILLON ◽  
...  
Keyword(s):  
Machine Learning ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Interferon Γ

scholarly journals Function of Cryopreserved Mesenchymal Stromal Cells With and Without Interferon-γ Prelicensing is Context Dependent

Stem Cells ◽  
2016 ◽  
Vol 35 (5) ◽  
pp. 1437-1439 ◽  
Author(s):  
Anthony J. Burand ◽  
Oliver W. Gramlich ◽  
Alex J. Brown ◽  
James A. Ankrum
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Interferon Γ ◽  
Context Dependent

Optimizing reporter constructs for in vivo bioluminescence imaging of interferon-γ stimulated mesenchymal stromal cells

2014 ◽  
Vol 42 (9) ◽  
pp. 793-803.e1 ◽  
Author(s):  
Jorge Perez-Galarza ◽  
Françoise Carlotti ◽  
Martijn J. Rabelink ◽  
Steve Cramer ◽  
Rob C. Hoeben ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Bioluminescence Imaging ◽  
Interferon Γ ◽  
In Vivo Bioluminescence Imaging

scholarly journals Pluripotency and Immunomodulatory Signatures of Canine Induced Pluripotent Stem Cell-derived Mesenchymal Stromal Cells Are Similar to Harvested Mesenchymal Stromal Cells

2020 ◽  
Author(s):  
Arash Shahsavari ◽  
Prasanna Weeratunga ◽  
Dmitry A. Ovchinnikov ◽  
Deanne Whitworth
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Induced Pluripotent Stem Cell ◽  
Interferon Γ ◽  
Mesenchymal Transition ◽  
Cox 2 ◽  
Induced Pluripotent ◽  
Tgf Β1

Abstract Background: With a view towards harnessing the therapeutic potential of canine mesenchymal stromal cells (cMSCs) as modulators of inflammation and the immune response, and to avoid the issues of the variable quality and quantity of harvested cMSCs, we examined the immunomodulatory properties of cMSCs derived from canine induced pluripotent stem cells (ciMSCs), and compared them to cMSCsharvested from adipose tissue (cAT-MSC) and bone marrow (cBM-MSC).Methods and results: Deep sequencing of the ciMSC transcriptome confirmed that ciMSCsexpress more genes in common with cBM-MSCsthan with the ciPSCs from which they were derived. Both ciMSCs and cBM-MSCsexpress a range of pluripotency factors in common withthe ciPSCsincluding NANOG, POU5F1 (OCT-4), SOX-2, KLF-4, LIN-28A, MYC, LIF, LIFR, and TERT. However, ESRRB and PRDM-14, both factors associated with naïve, rather than primed, pluripotency were expressed only in the ciPSCs. LOXL-2, which is involved in epithelial to mesenchymal transition (EMT), is also expressed in ciMSCs and cBM-MSCs but notciPSCs. ciMSCsconstitutively express the immunomodulatory factors iNOS, GAL-9, TGF-β1, PTGER-2αand VEGF, and the pro-inflammatory mediators COX-2,IL-1βand IL-8.When stimulated with the canine pro-inflammatory cytokines tumor necrosis factor-α (cTNF-α), interferon-γ (cIFN-γ), or a combination of both, ciMSCsupregulated their expression ofIDO,iNOS, GAL-9,HGF, TGF-β1, PTGER-2α, VEGF, COX-2, IL-1β andIL-8.When co-cultured with mitogen-stimulated lymphocytes, ciMSCsdownregulated their expression of iNOS, HGF, TGF-β1andPTGER-2α, while increasing their expression of COX-2, IDO and IL-1β. Conclusions: Taken together, these findings suggest that ciMSCs possess similar immunomodulatory capabilities as harvested cMSCs and support further investigation into the potential use ofciMSCsfor the management of canine immune-mediated and inflammatory disorders.

scholarly journals Mechanisms of T-Cell Immunosuppression by Mesenchymal Stromal Cells: What Do We Know So Far?

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Rodrigo Haddad ◽  
Felipe Saldanha-Araujo
Keyword(s):  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Types ◽  
Biological Properties ◽  
T Cell Response ◽  
Cell Contact ◽  
Inflammatory Microenvironment ◽  
And Function ◽  
Cellular Immune

Mesenchymal stromal cells (MSCs) are multipotent cells, which can give rise to several cell types including osteoblasts, adipocytes, and chondroblasts. These cells can be found in a variety of adult and fetal tissues, such as bone marrow, adipose tissue, cord blood, and placenta. In recent years, the biological properties of MSCs have attracted the attention of researchers worldwide due to their potential application for treating a series of clinical situations. Among these properties, special attention should be given to the immunoregulatory potential of those cells. MSCs are able to act on all cells of the immune system, which includes the capacity to inhibit the proliferation and function of T-cells. This feature renders them natural candidates to treat several diseases in which cellular immune response is exacerbated. In this review, we outline the main mechanisms by which MSCs immunosuppress T-cell response, focusing on cell-cell contact, secretion of soluble factors, and regulatory T-cell generation. The influence of surface markers in the immunosuppression process and features of MSCs isolated from different sources are also discussed. Finally, the influences of toll-like receptors and cytokines on the inflammatory microenvironment are highlighted regarding the activation of MSCs to exert their immunoregulatory function.

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