Abstract 12139: Unique Therapeutic Effect of Statin Nanoparticle-Loaded Adipose-Derived Stem Cells on Myocardial Infarction
Introduction: Clinical trials of autologous adipose-derived stem cell (AdSC) therapy for ischemic heart diseases (IHD) are now on-going. We have investigated the hypothesis that combination of AdSCs and statin, an agent with pleiotropic effects, could augment the therapeutic effect on myocardial infarction (MI).
Methods and Results: Human AdSC functions with different doses of simvastatin-conjugated nanoparticle (STNP) uptake were evaluated by in vitro assays. STNP significantly promoted the migration activity without changing the proliferation activity, and also up-regulated growth factors and vascular gene expressions peaking at 50μg/ml in AdSCs. Next, MI was induced by LAD ligation in nude mice, and the mice were assigned in the following groups with different treatments (tail vein injection) 3 days after MI: 1) PBS (control), 2) NP-AdSCs (104 cells), and 3) STNP-AdSCs (104 cells). Cardiac functional recovery assessed by echocardiography (EF and LVDd) was significantly improved at 4 weeks after surgery in STNP-AdSC group. Masson’s trichrome-stained sections revealed that the percent of LV fibrosis length was significantly reduced in STNP-AdSC group, and de novo muscle-like tissue was observed in infarct zone only in STNP-AdSC group. Although only a few transplanted AdSCs were detected by immunostaining with a human specific antibody for mitochondria in ischemic myocardium, a number of SM α-actin+ vessels/granulation as well as capillaries were observed in the pericardial site of infarct area in STNP-AdSC group. The histological finding is pretty unique in a mouse MI model. (Figure)
Conclusions: Intravenously injected small number (104/mouse) of statin nanoparticle-loaded hAdSCs exhibited a significant therapeutic effect with an intriguing histological finding on MI, giving rise to a novel therapeutic concept in autologous AdSC transplantation, specifically, in patients who have less number of AdSCs with IHD in clinical settings.
Author Disclosures: R. Yokoyama: None. M. Ii: None. Y. Tabata: None. M. Hoshiga: None. N. Ishizaka: None. M. Asahi: None.
- © 2014 by American Heart Association, Inc.