Development of novel cardiac regeneration therapy using a bio-drug delivery system

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08562
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Osaka Medical College
• Principal Investigator: Ii Masaaki 大阪医科大学, 研究支援センター, 講師 (10442922)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 心筋再生 / スタチン / 間葉系幹細胞 / DDS

Outline of Final Research Achievements

We have 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 up-regulated growth factor gene expression in vitro. A small number of intravenously administered SimNP-loaded AdSCs 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 WT-1 positive epicardial cells. These findings were attributed to the sustained, local simvastatin release from the recruited SimNP-loaded AdSCs in the infarcted myocardium. SimNP-loaded AdSCs may lead to a novel somatic stem cell therapy for IHDs.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

この研究成果によって、心筋梗塞を代表とする重症虚血性心疾患難治性心疾患に対する新たな心筋組織再生治療法を開発できる可能性がある。また、本治療技術が実用化されれば、簡便かつ安価な細胞製剤を心筋梗塞治療薬として利用できるため、欧米諸国や発展途上国などで開胸手術や心臓カテーテル治療などの高額医療を受けることができない患者に対しての福音となる可能性がある。さらに、AdSCは心血管系以外の細胞への分化能も有し、炎症巣や腫瘍にも集積する性質を持っているため、PLGAナノ粒子に含有させる薬剤を変更することによって、他疾患治療への波及効果もある点で意義深いと考える。