Mesenchymal Stromal Cells (MSC) : phenotypical and functional characterizations as tools for immunomodulation in Myasthenia Gravis

Autor: Bayer Wildberger, Alexandra, Villegas, José, Verdier, Julien, Giannini, Mariette, Maillard, Solène, Truffault, Frédérique, Corneau, Aurélien, Dragin, Nadine, Vanneaux, Valérie, Rouard, Hélène, Noël, Danièle, Martinaud, Christophe, Le Panse, Rozen, Berrih-Aknin, Sonia, Vilquin, J.-T
Přispěvatelé: Centre de Recherche en Myologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plateforme Cytométrie Pitié-Salpêtrière (LUMIC-CYPS), Unité Mixte de Service d'Imagerie et de Cytométrie [CHU Saint-Antoine] (UMS LUMIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Alloimmunité-Autoimmunité-Transplantation (A2T), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en Myologie – U974 SU-INSERM, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Myology 2019
Myology 2019, Mar 2019, Bordeaux, France
Popis: International audience; Several autoimmune diseases are mediated by antibodies produced after deregulations of the immune system and directed against self antigens. Myasthenia Gravis (MG) is a rare disease in which pathogenicity is due to autoantibodies directed against the neuromuscular endplate. MG is not really cured, corticosteroids and azathioprin are commonly used, however they trigger severe side-effects, mandating the setup of novel therapies. Mesenchymal Stromal/Stem Cells (MSC) are multipotent progenitor cells that can be isolated from various human tissues and can modulate the immune system via soluble mediators and cell-cell contacts. Our team has recently validated a new animal model of MG, in which we demonstrated that the transfer of MSC conditioned by peripheral blood mononucleated cells (PBMC) improved the clinical status of the animals (Sudres et al., JCI Insight 2017). To develop this immunomodulating approach in clinical perspective, we compared the phenotypes of research-grade (RG) and clinical-grade (CG) MSC testing a series of 60 antibodies (Ab) directed against surface antigens by flow cytometry. We evaluated the variations introduced by different conditioning treatments (activation by gamma-interferon, cross-stimulation by PBMC or monocytes). Markers involved in immunomodulation (recognition, activation, function of complement, co-stimulation, immune checkpoints) were increased or decreased depending on treatment. Adhesion molecules and receptors were also differentially modified (integrins, selectins, cell-cell adhesion molecules, growth factor receptors, tetraspanins). These results suggest that the conditioning regimens act through different pathways. From this panel, we derived a second one of 31 Ab allowing simultaneous labeling of MSC at single cell level by mass cytometry (CyTOF). We defined MSC clusters which were modulated upon activation. In parallel, we evaluated the functional activity of resting or conditioned CG MSC through a cell proliferation assay, and through the quantification by ELISA of secreted immunomodulating products. The conditioning regimens differentially modulated the secretion of Prostaglandin E2 and TGFbeta1, and inhibited PBMC proliferation. This work unveiled phenotypic and functional markers of MSC along with their modulations according to different treatments, and will contribute to validate a cell therapy product for immunomodulation purposes.
Databáze: OpenAIRE
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