Adipose Tissue-Derived Mesenchymal Stem Cells Have In Vivo Immunosuppressive Properties Applicable for the Control of the Graft-Versus-Host Disease

Authors

  • Rosa Yañez,

    1. Hematopoiesis and Gene Therapy Division, Centro de Investigaciones Energéticas, Medioambientales y Technologicas (CIEMAT)/Marcelino Botín Foundation, Madrid, Spain
    Search for more papers by this author
  • María Luisa Lamana,

    1. Hematopoiesis and Gene Therapy Division, Centro de Investigaciones Energéticas, Medioambientales y Technologicas (CIEMAT)/Marcelino Botín Foundation, Madrid, Spain
    Search for more papers by this author
  • Javier García-Castro,

    1. Pediatric Hematology & Oncology and Hematopoietic Transplant Unit, Hospital del Niño Jesús, Madrid, Spain
    Search for more papers by this author
  • Isabel Colmenero,

    1. Department of Pathology, Hospital del Niño Jesús, Madrid, Spain
    Search for more papers by this author
  • Manuel Ramírez,

    1. Pediatric Hematology & Oncology and Hematopoietic Transplant Unit, Hospital del Niño Jesús, Madrid, Spain
    Search for more papers by this author
  • Juan A. Bueren Ph.D.

    Corresponding author
    1. Hematopoiesis and Gene Therapy Division, Centro de Investigaciones Energéticas, Medioambientales y Technologicas (CIEMAT)/Marcelino Botín Foundation, Madrid, Spain
    • Hematopoiesis and Gene Therapy Division, CIEMAT, Avenida Complutense, no. 22, 28040 Madrid, Spain. Telephone: 34-91-346-6518; Fax: 34-91-346-6484
    Search for more papers by this author

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.

Ancillary