Cardiac Regeneration by Statin‐Polymer Nanoparticle‐Loaded Adipose‐Derived Stem Cell Therapy in Myocardial Infarction

Autor: Ryo Yokoyama, Masaaki Ii, Yasuhiko Tabata, Masaaki Hoshiga, Nobukazu Ishizaka, Michio Asahi
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Stem Cells Translational Medicine, Vol 8, Iss 10, Pp 1055-1067 (2019)
Druh dokumentu: article
ISSN: 2157-6580
2157-6564
DOI: 10.1002/sctm.18-0244
Popis: Abstract Clinical trials with autologous adipose‐derived stem cell (AdSC) therapy for ischemic heart diseases (IHDs) are ongoing. However, little is known about combinational therapeutic effect of AdSCs and statin poly(lactic‐co‐glycolic) acid (PLGA) nanoparticles on the ischemic myocardium. We investigated the hypothesis that statins, which have pleiotropic effects, augment the therapeutic potential of AdSCs and that AdSCs also act as drug delivery tools. Simvastatin‐conjugated nanoparticles (SimNPs) significantly promoted migration activity without changing proliferation activity and upregulated growth factor gene expression in vitro. A small number of intravenously administered SimNP‐loaded AdSCs (10,000 cells per mouse) improved cardiac function following myocardial infarction, inducing endogenous cardiac regeneration in the infarcted myocardium. The de novo regenerated myocardium was thought to be derived from epicardial cells, which were positive for Wilms' tumor protein 1 expression. These findings were attributed to the sustained, local simvastatin release from the recruited SimNP‐loaded AdSCs in the infarcted myocardium rather than to the direct contribution of recruited AdSCs to tissue regeneration. SimNP‐loaded AdSCs may lead to a novel somatic stem cell therapy for IHDs. Stem Cells Translational Medicine 2019;8:1055–1067
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