Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans

Lingyun Sun, Kentaro Akiyama, Huayong Zhang, Takayoshi Yamaza, Yayi Hou, Shengnan Zhao, Ting Xu, Anh Le, Songtao Shi

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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.

Original languageEnglish
Pages (from-to)1421-1432
Number of pages12
JournalSTEM CELLS
Volume27
Issue number6
DOIs
Publication statusPublished - Jun 1 2009

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Mesenchymal Stem Cell Transplantation
Systemic Lupus Erythematosus
Bone Marrow
Inbred MRL lpr Mouse
Salvage Therapy
Regulatory T-Lymphocytes
Therapeutics
Immunosuppressive Agents
Mesenchymal Stromal Cells
Cyclophosphamide
Immunosuppression
Glucocorticoids
Autoimmune Diseases
Homeostasis
Kidney

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. / Sun, Lingyun; Akiyama, Kentaro; Zhang, Huayong; Yamaza, Takayoshi; Hou, Yayi; Zhao, Shengnan; Xu, Ting; Le, Anh; Shi, Songtao.

In: STEM CELLS, Vol. 27, No. 6, 01.06.2009, p. 1421-1432.

Research output: Contribution to journalArticle

Sun, Lingyun ; Akiyama, Kentaro ; Zhang, Huayong ; Yamaza, Takayoshi ; Hou, Yayi ; Zhao, Shengnan ; Xu, Ting ; Le, Anh ; Shi, Songtao. / Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. In: STEM CELLS. 2009 ; Vol. 27, No. 6. pp. 1421-1432.
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