Abstract
Mesenchymal stem cells (MSC) have been used recently for the treatment of autoimmune diseases in murine animal models due to the immunoregulatory capacity. Current utilization of MSC requires cells in certain quantity with multiple courses of administration, leading to limitation in clinical usage. Here we efficiently treated collagen-induced arthritis rats with a single local implantation with reduced number of MSC (2∼20% of previous studies) with nano-fiber poly-lactic-co-glycolic acid (nano-fiber) scaffold. MSC seeded on nano-fiber scaffold suppressed arthritis and bone destruction due to inhibition of systemic inflammatory reaction and immune response by suppressing T cell proliferation and reducing anti- type II collagen antibody production. In vivo tracing of MSC demonstrated that these cells remained within the scaffold without migrating to other organs. Meanwhile, in vitro culture of MSC with nano-fiber scaffold significantly increased TGF-β1 production. These results indicate an efficient utilization of MSC with the scaffold for destructive joints in rheumatoid arthritis by a single and local inoculation. Thus, our data may serve as a new strategy for MSC-based therapy in inflammatory diseases and an alternative delivery method for bone destruction treatment.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Animals
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Arthritis, Experimental / immunology
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Arthritis, Experimental / therapy*
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CD4-Positive T-Lymphocytes / physiology
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Cell Proliferation
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Cytokines / metabolism
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Female
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Humans
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Lactic Acid / chemistry
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Mesenchymal Stem Cell Transplantation / methods*
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Mesenchymal Stem Cells / physiology*
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Nanofibers / chemistry
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Polyesters
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Polyglycolic Acid / chemistry
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Polymers / chemistry
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Rats, Inbred Lew
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Tissue Scaffolds / chemistry
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Transforming Growth Factor beta1 / metabolism
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Young Adult
Substances
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Cytokines
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Polyesters
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Polymers
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TGFB1 protein, human
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Transforming Growth Factor beta1
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Polyglycolic Acid
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Lactic Acid
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poly(lactide)
Grants and funding
This work was supported in part by Research Grants-In-Aid for Scientific Research from the Ministry of Health, Labor and Welfare of Japan, the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the University of Occupational and Environmental Health, Japan and UOEH Grant for Advanced Research. Hiroaki Kaneko, Makoto Satake and Yuka Yamamoto are employees of the Teijin Limited. Masahiro Kondo is employee of the Mitsubishi Tanabe Pharma Corporation. Teijin Limited and Mitsubishi Tanabe Pharma Corporation provided support in the form of salaries for authors HK, MS, YY and MK, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.