Reversal of serologic, immunologic, and histologic dysfunction in mice with systemic lupus erythematosus by long-term serial adipose tissue-derived mesenchymal stem cell transplantation.

Abstract

OBJECTIVE:

To investigate the efficacy of human adipose tissue-derived mesenchymal stem cell (AD-MSC) transplantation in systemic lupus erythematosus (SLE) and to determine the optimal transplantation window for stem cells either before or after disease onset.

METHODS:

(NZB×NZW)F1 mice with SLE were administered human AD-MSCs (5×10(5)) intravenously every 2 weeks from age 6 weeks until age 60 weeks, while the control group received saline vehicle on the same schedule. Another experiment was carried out with a different initiation time point for serial transplantation (age 6 weeks or age 32 weeks).

RESULTS:

Long-term serial administration (total of 28 times) of human AD-MSCs ameliorated SLE without any adverse effects. Compared with the control group, the human AD-MSC-treated group had a significantly higher survival rate with improvement of histologic and serologic abnormalities and immunologic function, and also had a decreased incidence of proteinuria. Anti-double-stranded DNA antibodies and blood urea nitrogen levels decreased significantly with transplantation of human AD-MSCs, and serum levels of granulocyte-macrophage colony-stimulating factor, interleukin-4 (IL-4), and IL-10 increased significantly. A significant increase in the proportion of CD4+FoxP3+ cells and a marked restoration of capacity for cytokine production were observed in spleens from the human AD-MSC-treated group. In the second experiment, an early stage treatment group showed better results (higher survival rates and lower incidence of proteinuria) than an advanced stage treatment group.

CONCLUSION:

Serial human AD-MSC transplantation had beneficial effects in the treatment of SLE, without adverse effects. Transplantation of human AD-MSCs before disease onset was preferable for amelioration of SLE and restoration of immune homeostasis.

• Authors: Eun Wha Choi, Il Seob Shin, So Young Park, Ji Hyun Park, Jong Sung Kim, Eun Ji Yoon, Sung Keun Kang, Jeong Chan Ra, Sung Hwa Hong
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 64 Issue 1 Pg. 243-53 (Jan 2012) ISSN: 1529-0131 [Electronic] United States
• PMID: 21904997 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 by the American College of Rheumatology.

Chemical References

• Antibodies, Antinuclear
• Cytokines

Topics

• Adipose Tissue (cytology)
• Animals
• Antibodies, Antinuclear (immunology, metabolism)
• Cell Count
• Cytokines (metabolism)
• Disease Models, Animal
• Disease Progression
• Female
• Humans
• Longevity
• Lupus Erythematosus, Systemic (immunology, pathology, prevention & control)
• Lupus Nephritis (immunology, pathology, prevention & control)
• Mesenchymal Stem Cell Transplantation
• Mice
• Organ Size
• Proteinuria (immunology, pathology, prevention & control)
• Spleen (metabolism, pathology)
• T-Lymphocytes, Regulatory (immunology, pathology)
• Time Factors
• Transplantation, Heterologous