title: Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease.
abstract: Previous studies have shown the relevance of bone marrow-derived MSCs (BM-MSCs) in controlling graft-versus-host disease (GVHD) after allogeneic transplantation. Since adipose tissue-derived MSCs (Ad-MSCs) may constitute a good alternative to BM-MSCs, we have expanded MSCs derived from human adipose tissue (hAd-MSCs) and mouse adipose tissue (mAd-MSCs), investigated the immunoregulatory properties of these cells, and evaluated their capacity to control GVHD in mice. The phenotype and immunoregulatory properties of expanded hAd-MSCs were similar to those of human BM-MSCs. Moreover, hAd-MSCs inhibited the proliferation and cytokine secretion of human primary T cells in response to mitogens and allogeneic T cells. Similarly, ex vivo expanded mAd-MSCs had an equivalent immunophenotype and exerted immunoregulatory properties similar to those of hAd-MSCs. Moreover, the infusion of mAd-MSCs in mice transplanted with haploidentical hematopoietic grafts controlled the lethal GVHD that occurred in control recipient mice. These findings constitute the first experimental proof that Ad-MSCs can efficiently control the GVHD associated with allogeneic hematopoietic transplantation, opening new perspectives for the clinical use of Ad-MSCs.
authors.affiliation: Hematopoiesis and Gene Therapy Division, Centro de Investigaciones Energéticas, Medioambientales y Technologicas (CIEMAT)/Marcelino Botín Foundation, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Yañez
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Lamana
authors.forename: Javier
authors.initials: J
authors.lastname: García-Castro
authors.forename: Isabel
authors.initials: I
authors.lastname: Colmenero
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramírez
authors.forename: Juan A
authors.initials: JA
authors.lastname: Bueren
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology*; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000187:drug effects; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D008934:Mitogens; D010835:Phytohemagglutinins