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Tissue-Specific Stem Cells
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Mesenchymal Stem Cell Transplantation Reverses Multiorgan Dysfunction in Systemic Lupus Erythematosus Mice and Humans†‡
Article first published online: 19 MAR 2009
DOI: 10.1002/stem.68
Copyright © 2009 AlphaMed Press
Additional Information
How to Cite
Sun, L., Akiyama, K., Zhang, H., Yamaza, T., Hou, Y., Zhao, S., Xu, T., Le, A. and Shi, S. (2009), Mesenchymal Stem Cell Transplantation Reverses Multiorgan Dysfunction in Systemic Lupus Erythematosus Mice and Humans. STEM CELLS, 27: 1421–1432. doi: 10.1002/stem.68
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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.
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First published online in STEM CELLSExpress March 19, 2009
Publication History
- Issue published online: 1 JUN 2009
- Article first published online: 19 MAR 2009
- Accepted manuscript online: 19 MAR 2009 12:00AM EST
- Manuscript Accepted: 6 MAR 2009
- Manuscript Received: 5 JAN 2009
Funded by
- California Institute for Regenerative Medicine. Grant Number: RN1-00572
- NIDCR/NIH. Grant Numbers: R01DE017449, R21 DE017632
- National Natural Science Foundation of China. Grant Number: 30772014
- Chinese Education Ministry. Grant Number: 20050315001
- Jiangsu Province 135 Talent Foundation. Grant Number: RC2007002
Keywords:
- Bone marrow mesenchymal stem cells;
- Transplantation;
- Systemic lupus erythematosus
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