title: Human mesenchymal stem cells derived from induced pluripotent stem cells down-regulate NK-cell cytolytic machinery.
abstract: A major issue in immunosuppressive biotherapy is the use of mesenchymal stem cells (MSCs) that harbor regulatory capacity. However, currently used bone marrow-derived MSCs (BM-MSCs) are short-lived and cannot assure long lasting immunoregulatory function both in vitro and in vivo. Consequently, we have generated MSCs from human induced pluripotent stem (IPS-MSCs) cells that share similar properties with embryonic stem cells (ES-MSCs). Herein, we compared the immunoregulatory properties of ES/IPS-MSCs with those of BM-MSCs and showed, for the first time, that IPS-derived MSCs display remarkable inhibition of NK-cell proliferation and cytolytic function in a similar way to ES-MSCs. Both MSCs disrupt NK-cell cytolytic machinery in the same fashion that BM-MSCs, by down-regulating the expression of different activation markers and ERK1/2 signaling, leading to an impairment to form immunologic synapses with target cells and, therefore, secretion of cytotoxic granules. In addition, they are more resistant than adult BM-MSCs to preactivated NK cells. IPS-MSCs could represent an attractive alternative source of immunoregulatory cells, and their capacity to impair NK-cell cytotoxicity constitutes a complex mechanism to prevent allograft rejection.
authors.affiliation: Unité Mixte de Reccherche (UMR) 1014 Inserm, Université Paris Sud 11, Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris (AP-HP), Villejuif, France.
authors.forename: Massimo
authors.initials: M
authors.lastname: Giuliani
authors.forename: Noufissa
authors.initials: N
authors.lastname: Oudrhiri
authors.forename: Zaeem M
authors.initials: ZM
authors.lastname: Noman
authors.forename: Amelia
authors.initials: A
authors.lastname: Vernochet
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
authors.forename: Bruno
authors.initials: B
authors.lastname: Azzarone
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
authors.forename: Annelise
authors.initials: A
authors.lastname: Bennaceur-Griscelli
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D001853:Bone Marrow / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D015536:Down-Regulation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D006084:Graft Rejection / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D016086:Lentivirus; D008213:Lymphocyte Activation / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D014161:Transduction, Genetic
chemical_list: C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3