Mesenchymal Stem Cell Transplantation Reverses Multiorgan Dysfunction in Systemic Lupus Erythematosus Mice and Humans

Authors

  • Lingyun Sun,

    Corresponding author
    1. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
    • Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, China
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    • Telephone: 0118613705186409; Fax: 011862583105209

  • Kentaro Akiyama,

    1. Center for Craniofacial Molecular Biology, University of Southern California School of Dentistry, Los Angeles, California, USA
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  • Huayong Zhang,

    1. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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  • Takayoshi Yamaza,

    1. Center for Craniofacial Molecular Biology, University of Southern California School of Dentistry, Los Angeles, California, USA
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  • Yayi Hou,

    1. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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  • Shengnan Zhao,

    1. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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  • Ting Xu,

    1. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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  • Anh Le,

    1. Center for Craniofacial Molecular Biology, University of Southern California School of Dentistry, Los Angeles, California, USA
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  • Songtao Shi

    Corresponding author
    1. Center for Craniofacial Molecular Biology, University of Southern California School of Dentistry, Los Angeles, California, USA
    • Center for Craniofacial Molecular Biology, University of Southern California, Health Sciences Campus, 2,250 Alcazar Street, CSA103, Los Angeles, California 90,033, USA
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    • Telephone: 0118613705186409; Fax: 011862583105209


  • Author contributions: L.S.: conception and design, data analysis and interpretation; K.A.: collection and/or assembly of data, data analysis and interpretation; H.Z.: provision of study material or patients, collection, and/or assembly of data; T.Y.: collection and/or assembly of data, data analysis and interpretation; Y.H.: data analysis and interpretation; S.Z.: collection and/or assembly of data; T.X.: collection and/or assembly of data; A.L. and S.S.: conception and design, data analysis and interpretation, manuscript writing. L.S. and K.A. contributed equally to this article.

  • First published online in STEM CELLSExpress March 19, 2009

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that, despite the advances in immunosuppressive medical therapies, remains potentially fatal in some patients, especially in treatment-refractory patients. Here, we reported that impairment of bone marrow mesenchymal stem cells (BMMSCs) and their associated osteoblastic niche deficiency contribute in part to the pathogenesis of SLE-like disease in MRL/lpr mice. Interestingly, allogenic BMMSC transplantation (MSCT) is capable of reconstructing the bone marrow osteoblastic niche and more effectively reverses multiorgan dysfunction when compared with medical immunosuppression with cyclophosphamide (CTX). At the cellular level, MSCT, not CTX treatment, was capable to induce osteoblastic niche reconstruction, possibly contributing to the recovery of regulatory T-cells and reestablishment of the immune homeostasis. On the basis of the promising clinical outcomes in SLE mice, we treated four CTX/glucocorticoid treatment-refractory SLE patients using allogenic MSCT and showed a stable 12–18 months disease remission in all treated patients. The patients benefited an amelioration of disease activity, improvement in serologic markers and renal function. These early evidences suggest that allogenic MSCT may be a feasible and safe salvage therapy in refractory SLE patients. STEM CELLS 2009;27:1421–1432

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