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BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) modulate the immune response and represent a potential treatment for inflammatory and autoimmune diseases. We hypothesized that this feature could be potentiated by co-administering anti-inflammatory cytokines. In this article, we asked whether engineering of Wharton Jelly-derived human MSCs (WJ-hMSCs) to express an anti-inflammatory cytokine increases cell immunomodulatory properties without altering their native features. METHODS: We used Epstein-Barr virus-derived interleukin-10 (vIL-10), which shares some immunosuppressive properties with human IL-10 but lacks immunostimulatory activity. Engineering was accomplished by transducing WJ-hMSCs with a self-inactivating feline immunodeficiency virus-derived vector co-expressing vIL-10 and herpes simplex virus type-1 thymidine kinase (TK). TK was added to allow future tracking of WJ-hMSC in vivo by positron electron tomography (PET). RESULTS: The results show that (i) expression of TK and/or vIL-10 does not change WJ-hMSC phenotypic and functional properties; (ii) vIL-10 is secreted, biologically active and enhances the immunosuppressing functions of WJ-hMSCs; (iii) v-IL10 and TK can be produced simultaneously by the same cells and do not interfere with each other. DISCUSSION: WJ-hMSCs engineered to secrete vIL-10 could be a powerful tool for adoptive cell therapy of immune-mediated diseases, and therefore, additional studies are warranted to confirm their efficacy in suitable animal disease models.

Original publication

DOI

10.1016/j.jcyt.2015.11.011

Type

Journal article

Journal

Cytotherapy

Publication Date

02/2016

Volume

18

Pages

205 - 218

Keywords

ELISpot, bicistronic vector, immunosuppression, interferon-γ, lentiviral vectors, thymidine kinase, umbilical cord mesenchymal stromal cells, viral interleukin 10, Animals, Cell Line, HEK293 Cells, Herpesvirus 4, Human, Humans, Immunodeficiency Virus, Feline, Immunosuppression, Immunosuppressive Agents, Immunotherapy, Adoptive, Interleukin-10, Mesenchymal Stromal Cells, Thymidine Kinase, Wharton Jelly