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Title: In Vivo Interleukin-13-Primed Macrophages Contribute to Reduced Alloantigen-Specific T Cell Activation and Prolong Immunological Survival of Allogeneic Mesenchymal Stem Cell Implants
Authors: Hoornaert, Chloe J.
Luyckx, Evi
Reekmans, Kristien
Dhainaut, Maxime
Guglielmetti, Caroline
Le Blon, Debbie
Dooley, Dearbhaile
Fransen, Erik
Daans, Jasmijn
Verbeeck, Louca
Quarta, Alessandra
De Vocht, Nathalie
Lemmens, Evi
Goossens, Herman
Van der Linden, Annemie
Roobrouck, Valerie D.
Verfaillie, Catherine
Hendrix, Sven
Moser, Muriel
Berneman, Zwi N.
Ponsaerts, Peter
Issue Date: 2016
Citation: STEM CELLS, 34(7), p. 1971-1984
Abstract: Transplantation of mesenchymal stem cells (MSCs) into injured or diseased tissuefor the in situ delivery of a wide variety of MSC-secreted therapeutic proteinsis an emerging approach for the modulation of the clinical course of several diseases and traumata. From an emergency point-of-view, allogeneic MSCs have numerous advantages over patient-specific autologous MSCs since off-the-shelf cell preparations could be readily available for instant therapeutic intervention following acute injury. Although we confirmed the in vitro immunomodulatory capacity of allogeneic MSCs on antigen-presenting cells with standard coculture experiments, allogeneic MSC grafts were irrevocably rejected by the host's immune system upon either intramuscular or intracerebral transplantation. In an attempt to modulate MSC allograft rejection in vivo, we transduced MSCs with an interleukin-13 (IL13)-expressing lentiviral vector. Our data clearly indicate that prolonged survival of IL13-expressing allogeneic MSC grafts in muscle tissue coincided with the induction of an alternatively activated macrophage phenotype in vivo and a reduced number of alloantigen-reactive IFN- and/or IL2-producing CD8(+) T cells compared to nonmodified allografts. Similarly, intracerebral IL13-expressing MSC allografts also exhibited prolonged survival and induction of an alternatively activated macrophage phenotype, although a peripheral T cell component was absent. In summary, this study demonstrates that both innate and adaptive immune responses are effectively modulated in vivo by locally secreted IL13, ultimately resulting in prolonged MSC allograft survival in both muscle and brain tissue.
Notes: [Hoornaert, Chloe J.; Luyckx, Evi; Reekmans, Kristien; Le Blon, Debbie; Daans, Jasmijn; Verbeeck, Louca; Quarta, Alessandra; De Vocht, Nathalie; Berneman, Zwi N.; Ponsaerts, Peter] Univ Libre Bruxelles, Lab Expt Hematol, Gosselies, Belgium. [Hoornaert, Chloe J.; Luyckx, Evi; Reekmans, Kristien; Le Blon, Debbie; Daans, Jasmijn; Verbeeck, Louca; Quarta, Alessandra; De Vocht, Nathalie; Goossens, Herman; Berneman, Zwi N.; Ponsaerts, Peter] Univ Libre Bruxelles, Vaccine & Infect Dis Inst, Gosselies, Belgium. [Guglielmetti, Caroline; Van der Linden, Annemie] Univ Libre Bruxelles, Bioimaging Lab, Gosselies, Belgium. [Dhainaut, Maxime; Moser, Muriel] Univ Libre Bruxelles, Dept Mol Biol, Immunobiol Lab, Gosselies, Belgium. [Dooley, Dearbhaile; Lemmens, Evi; Hendrix, Sven] Hasselt Univ, Biomed Res Inst, Dept Morphol, Diepenbeek, Belgium. [Fransen, Erik] Univ Antwerp, StatUa Ctr Stat, Antwerp, Belgium. [Roobrouck, Valerie D.; Verfaillie, Catherine] Katholieke Univ Leuven, Stem Cell Inst, Stem Cell Biol & Embryol Unit, Leuven, Belgium.
URI: http://hdl.handle.net/1942/22061
DOI: 10.1002/stem.2360
ISI #: 000379902900022
ISSN: 1066-5099
Category: A1
Type: Journal Contribution
Validation: ecoom, 2017
Appears in Collections: Research publications

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