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Author: search.filters.author.Maroun KhourySubject: search.filters.subject.animal

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    Time-dependent LPS exposure commands MSC immunoplasticity through TLR4 activation leading to opposite therapeutic outcome in EAE
    (2020)
    Mónica Kurte
    ;
    Ana María Vega-Letter
    ;
    Patricia Luz-Crawford
    ;
    Farida Djouad
    ;
    Danièle Noël
    <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Mesenchymal stem cells (MSCs) have been recognized for their regenerative and anti-inflammatory capacity which makes them very attractive to cell therapy, especially those ones to treat inflammatory and autoimmune disease. Two different immune-phenotypes have been described for MSCs depending on which Toll-like receptor (TLR) is activated. MSC1 is endowed with a pro-inflammatory phenotype following TLR4 activation with LPS. On the other hand, anti-inflammatory MSC2 is induced by the activation of TLR3 with Poly(I:C). High immunoplasticity of MSCs is a matter of concern in cell-based therapies. In this study, we investigated whether a single stimulus can induce both types of MSCs through a differential activation of TLR4 with LPS.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>MSCs were activated with LPS following a short exposure of 1-h (MSCs-LPS1h) or long-time exposure for 48 h (MSCs-LPS48h), and then, we evaluated the biological response in vitro, the immunosuppressive capacity of MSCs in vitro, and the therapeutic potential of MSCs in an experimental autoimmune encephalomyelitis (EAE) mouse model.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Our results showed that 1-h LPS exposure induced a MSC1 phenotype. Indeed, MSCs-LPS1h expressed low levels of NO/iNOS and decreased immunosuppressive capacity in vitro without therapeutic effect in the EAE model. In contrast, MSCs-LPS48h achieved a MSC2-like phenotype with significant increase in the immunosuppressive capacity on T cell proliferation in vitro, together with an improved in the therapeutic effect and higher Treg, compared to unstimulated MSCs. Furthermore, we determine through the MSCs-TLR4KO that the expression of TLR4 receptor is essential for MSCs’ suppressive activity since TLR4 deletion was associated with a diminished suppressive effect in vitro and a loss of therapeutic effect in vivo.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>We demonstrate that MSCs display a high immunoplasticity commanded by a single stimulus, where LPS exposure time regulated the MSC suppressive effect leading into either an enhanced or an impairment therapeutic activity. Our results underscore the importance of phenotype conversion probably related to the TLR4 expression and activation, in the design of future clinical protocols to treat patients with inflammatory and autoimmune diseases.</jats:p> </jats:sec>
      7Scopus© Citations 60
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    Exosomes on the border of species and kingdom intercommunication
    (2019)
    SCHUH, CHRISTINA  
    ;
    Jimena Cuenca
    ;
    Francisca Alcayaga-Miranda
    ;
    Maroun Khoury
      1Scopus© Citations 48  4
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    Stem cell exosomes inhibit angiogenesis and tumor growth of oral squamous cell carcinoma
    (2019)
    Leonie Rosenberger
    ;
    EZQUER, EDUARDO MARCELO  
    ;
    Fernando Lillo-Vera
    ;
    Paulina L. Pedraza
    ;
    María Ignacia Ortúzar
      12Scopus© Citations 125
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    Exosome-like vesicles in Apis mellifera bee pollen, honey and royal jelly contribute to their antibacterial and pro-regenerative activity
    (2019)
    Christina M. A. P. Schuh
    ;
    Sebastian Aguayo
    ;
    Gabriela Zavala
    ;
    Maroun Khoury
    <jats:p>Microvesicles have become key players in cellular communication. Since glandular secretions present a rich source of active exosomes, we hypothesized that exosome-like vesicles are present in Apis mellifera hypopharyngeal gland secretomal products (honey, royal jelly and bee pollen), and participate in their known antibacterial and pro-regenerative effects. We developed an isolation protocol based on serial- and ultracentrifugation steps and demonstrated the presence of protein-containing exosome-like vesicles in all three bee-derived products. Assessing their antibacterial properties, we found that exosome-like vesicles had bacteriostatic, bactericidal and biofilm-inhibiting effects on Staphylococcus aureus. Furthermore, we could demonstrate that mesenchymal stem cells (MSCs) internalize bee-derived exosome-like vesicles and that these vesicles influence their migration potential. In an in vitro wound healing assay, honey and royal jelly exosome-like vesicles increased migration of human MSC, demonstrating their interkingdom activity. Summarizing, we have discovered exosome-like vesicles as a new, active compound in bee pollen, honey and royal jelly.</jats:p>
    Scopus© Citations 49  1