Interferon γ induced compositional changes in human bone marrow derived mesenchymal stem/stromal cells

Abstract

BackgroundMesenchymal stem/stromal cells (MSC) display a range of immunoregulatory properties which can be enhanced by the exposure to cytokines such interferon γ (IFN-γ). However the compositional changes associated with the ‘licensing’ of these cells have not been clearly defined. The present study was undertaken to provide a detailed comparative proteomic analysis of the compositional changes that occur in human bone marrow derived MSC following 20 h treatment with IFN-γ.Methods2D LC MSMS analysis of control and IFN-γ treated cells from 5 different healthy donors provided confident identification of more than 8400 proteins.ResultsIn total 210 proteins were shown to be significantly altered in their expression levels (≥|2SD|) following IFN-γ treatment. The changes for several of these proteins were confirmed by flow cytometry. STRING analysis determined that approximately 30% of the altered proteins physically interacted in described interferon mediated processes. Comparison of the list of proteins that were identified as changed in the proteomic analysis with data for the same proteins in the Interferome DB indicated that ~35% of these proteins have not been reported to be IFN-γ responsive in a range of cell types.ConclusionsThis data provides an in depth analysis of the proteome of basal and IFN-γ treated human mesenchymal stem cells and it identifies a number of novel proteins that may contribute to the immunoregulatory capacity if IFN-γ licensed cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-017-9161-1) contains supplementary material, which is available to authorized users.

Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies

“…In comparative proteomic analyses of human bone marrow-derived MSC (BM-MSC) primed with IFN-γ, 210 proteins with significantly altered expressions were identified, 169 of which were overexpressed (for example IDO, PDL-1, ICAM-1, VCAM-1, and BST-2) and 41 downregulated (for example ANTXR1, APCDD1L, NPR3, FADS2) [ 22 ].…”

Anti‐donor antibody induction following intramuscular injections of allogeneic mesenchymal stromal cells

“…The results we report here demonstrate that anti‐donor IgG antibodies induced by single or repeated injections of allo‐MSC – in this case by the IM route – bind specifically to MSC and are directed against IFNγ‐regulated cell surface allo‐antigens. Although preactivation (“licensing”) of MSC with IFNγ has been shown in in vitro and in vivo studies to be associated with enhanced immunomodulatory properties, IFNγ is also known to induce expression of surface proteins such as MHC I, MHC II, B7‐H1 and ICAM‐1 that could serve as allo‐antigens and/or enhance immunogenicity . Although we did not formally identify the IFNγ‐inducible proteins that served as targets for anti‐donor IgG in the serum of BALB/c mice following IM injection of B6 MSC, it is likely that these predominantly represent strain‐specific MHC I and MHC II.…”

Augmentation of Antibacterial Activity in Mesenchymal Stromal Cells Through Systems-Level Analysis and CRISPR-mediated Activation of CD14

“…For example, exposure of MSCs to hypoxia and serum deprivation (a condition that mimicks in vivo administration of these cells) leads to metabolic and lipidomic reprogramming, as well as increased production of exosomes packed with immunomodulatory metabolites 28–30 . In another example, priming MSCs with cytokines can direct large-scale changes to the MSC proteome and secretome that impact inflammation and angiogenesis 31,32 . Importantly, these priming stimuli in vitro can create enduring alterations in MSC phenotypes which persist even upon transition to a new environment, including in vivo contexts; this suggests that “priming” may be an effective strategy for manipulating MSC behavior for therapeutic purposes 26,33 .…”