Statin-polymer nanoparticles enhance the anti-inflammatory and anti-fibrotic effects of adipose-derived stem cell transplantation in a mouse model of bleomycin-induced scleroderma

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15761
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Osaka Medical College
• Principal Investigator: Nagai Koji 大阪医科大学, 医学部, 非常勤医師 (30572458)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 強皮症 / 脂肪幹細胞 / 間質性肺炎

Outline of Final Research Achievements

This study investigated the effects of simvastatin-conjugated nanoparticles (SimNPs) on the functions of adipose-derived mesenchymal stem cells (AdSCs) and the therapeutic effect of SimNP-AdSCs in mice models of scleroderma. The cellular functions of AdSCs from Balb/c mice conjugated with different concentrations of statins was observed, and the optimum simvastatin dose was selected. Mice were assigned to four groups: bleomycin (BLM) alone group, NP-AdSC group, SimNP group, and SimNP-AdSC group, and the treatments were performed on day 7. SimNPs significantly promoted migration activity, viability, and up-regulated immunomodulatory factors in in vitro assays. Inflammation and fibrosis in skin were significantly supressed in the SimNP-AdSC group. The gene expression levels of TNF-alpha and IL-4 were significantly lower and the MMP-9/TIMP-1 ratio was higher in the SimNP-AdSC group than the NP-AdSC group.

Free Research Field

膠原病

Academic Significance and Societal Importance of the Research Achievements

本研究の結果から、SimNP-AdSCsはAdSCs単独より高い抗炎症効果と抗線維化効果が得られたことから、強皮症や合併する臓器病変である間質性肺炎に対する将来的に有望な治療候補になり得る可能性がある。この結果は、AdSCsの投与細胞数を減らし肺塞栓のリスク低減につながるという点で、より臨床応用に近づいたと言えるのではないか。AdSCsの細胞機能を更に高める方法の開発が今後も求められる。