THU0338 SIMVASTATIN-CONJUGATED NANOPARTICLE ENHANCES THE THERAPEUTIC EFFECT OF ADIPOSE-DERIVED STEM CELLS ON INTERSTITIAL LUNG DISEASE

Background: Interstitial lung disease (ILD) associated with connective tissue disease is a life-threatening pathological condition that causes respiratory failure when it progresses. Lung inflammation is treated with corticosteroids and immunosuppressants, and pulmonary fibrosis is treated with anti-fibrosis agents such as pirfenidone and nintedanib. However, many cases are treatment-resistant and the outcome is poor. Moreover, adverse effects such as infections resulting from immunosuppressive therapy are problematic. The development of new treatments is thus required for ILD from the viewpoint of the poor effect and adverse effects of the currently available treatments. Research and development with adipose-derived stem cells (AdSCs) in immunosuppressive therapy have progressed for autoimmune diseases, and favorable outcomes have been reported. In recent years, the effectiveness of AdSCs in ILD model mice has been demonstrated (ref). The statin preparation has not only an angiogenesis promoting action, an immunosuppressive action, an anti-fibrotic action but also an action of promoting a cellular function including a migratory ability. Objectives: We have investigated the hypothesis that statin, an agent with pleiotropic effects, could augment the therapeutic potential of AdSCs. Methods: ILD was induced by bleomycin (BLM) in C57BL/6 mouse, and the mice were assigned in the following groups: 1) Control, 2) NP-AdSCs (2.5×104 cells), and 3) STNP-AdSCs (2.5×104 cells). Results: Simvastatin-conjugated nanoparticles (STNP) significantly promoted the migration activity and cell survival without changing the proliferation activity, and up-regulated transforming growth factor (TGF) -β1 in vitro assays. Lung inflammation and fibrosis assessed were significantly supressed at 4 weeks after starting BLM administration in STNP-AdSCs group (Figure). The levels of IL-4, IFN-gamma, TNF-alpha, COL1A1, and TIMP1 mRNA expression at 28 days after BLM administration were significantly lower in STNP-AdSCs group compared with that in other groups. Conclusion: Simvastatin-conjugated nanoparticles enhanced the therapeutic effect of a small number of AdSCs transplantation. Reference: [1] Sci Rep 6; 7 (1): 14608, 2017. Acknowledgement: This study was supported by Grants-in-Aid for Scientific Research-KAKENHI- of Japan (18K08160). Disclosure of Interests: None declared