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TRANSLATIONAL AND CLINICAL RESEARCH |
aHematopoiesis and Gene Therapy Division, Centro de Investigaciones Energéticas, Medioambientales y Technologicas (CIEMAT)/Marcelino Botín Foundation, Madrid, Spain;
bPediatric Hematology & Oncology and Hematopoietic Transplant Unit and
cDepartment of Pathology, Hospital del Niño Jesús, Madrid, Spain
Key Words. Stem cell transplantation • Graft-versus-host disease • Immunosuppression • Mesenchymal stem cells • Experimental model
Correspondence: Juan A. Bueren, Ph.D., Hematopoiesis and Gene Therapy Division, CIEMAT, Avenida Complutense, no. 22, 28040 Madrid, Spain. Telephone: 34-91-346-6518; Fax: 34-91-346-6484; e-mail: juan.bueren{at}ciemat.es
Received on April 17, 2006;
accepted for publication on July 11, 2006.
First published online in STEM CELLS EXPRESS July 27, 2006.
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.
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