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Rheumatology Advance Access originally published online on March 3, 2008
Rheumatology 2008 47(4):454-457; doi:10.1093/rheumatology/ken058
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Mouse model of dermal fibrosis induced by one-time injection of bleomycin-poly(L-lactic acid) microspheres

Y. Shibusawa1, I. Negishi1, Y. Tabata2 and O. Ishikawa1

1Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Gunma and 2Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.

Correspondence to: Y. Shibusawa, Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. E-mail: yshibusa{at}showa.gunma-u.ac.jp


  Abstract

Objective. Animal models are useful tools to study various aspects of human diseases. Bleomycin (BLM)-induced scleroderma mouse has been widely investigated as an animal model of scleroderma. Repeated injections of BLM, either daily or every other day, for 3–4 weeks are required to induce scleroderma in mice. Poly(L-lactic acid) (PLA) is a biodegradable, biocompatible and bioabsorbable device that has been widely investigated for controlled drug release. In this study, we fabricated BLM-containing PLA microspheres and subcutaneously injected them into C3H mice for only one time.

Methods. Treated skins were harvested at days 7 and 21. Then, histological examination and collagen content measurement assay were performed. The mRNA expression of {alpha}1(I) collagen (COL1A1), monocyte chemoattractant protein-1 (MCP-1), TGF-β1 and connective tissue growth factor (CTGF) were quantified by real-time PCR.

Results. Dermal fibrosis was histologically observed at day 7 after injection and remained present at day 21. Tissue responses against BLM-PLA microspheres alone were mild. Soluble collagen content and expression level of {alpha}1(I) collagen mRNA were significantly elevated at day 21. Expression levels of MCP-1 mRNA and TGF-β1 mRNA at day 7 and CTGF mRNA at day 21 were also elevated.

Conclusion. The present study demonstrated for the first time that one-time injection of BLM-PLA microspheres can induce dermal fibrosis in C3H mice. BLM-PLA microspheres thus offer a labour-saving, simple and powerful tool to establish an animal model of BLM-induced dermal fibrosis.

KEY WORDS: Bleomycin, Scleroderma, Mouse model, Dermal fibrosis, Drug delivery system, Poly(L-lactic acid)

Submitted 11 October 2007; revised version accepted 24 January 2008.
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