caa a22 4500 605478945 CHVBK 20210128100408.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s10741-015-9477-8 doi (NATIONALLICENCE)springer-10.1007/s10741-015-9477-8 A sustained-release drug-delivery system of synthetic prostacyclin agonist, ONO-1301SR: a new reagent to enhance cardiac tissue salvage and/or regeneration in the damaged heart [Elektronische Daten] [Satsuki Fukushima, Shigeru Miyagawa, Yoshiki Sakai, Yoshiki Sawa] Cardiac failure is a major cause of mortality and morbidity worldwide, since the standard treatment for cardiac failure in the clinical practice is chiefly to focus on removal of insults against the heart or minimisation of additional factors to exacerbate cardiac failure, but not on regeneration of the damaged cardiac tissue. A synthetic prostacyclin agonist, ONO-1301, has been developed as a long-acting drug for acute and chronic pathologies related to regional ischaemia, inflammation and/or interstitial fibrosis by pre-clinical studies. In addition, poly-lactic co-glycolic acid-polymerised form of ONO-1301, ONO-1301SR, was generated to achieve a further sustained release of this drug into the targeted region. This unique reagent has been shown to act on fibroblasts, vascular smooth muscle cells and endothelial cells in the tissue via the prostaglandin IP receptor to exert paracrinal release of multiple protective factors, such as hepatocyte growth factor, vascular endothelial growth factor or stromal cell-derived factor-1, into the adjacent damaged tissue, which is salvaged and/or regenerated as a result. Our laboratory developed a new surgical approach to treat acute and chronic cardiac failure using a variety of animal models, in which ONO-1301SR is directly placed over the cardiac surface to maximise the therapeutic effects and minimise the systemic complications. This review summarises basic and pre-clinical information of ONO-1301 and ONO-1301SR as a new reagent to enhance tissue salvage and/or regeneration, with a particular focus on the therapeutic effects on acute and chronic cardiac failure and underlying mechanisms, to explore a potential in launching the clinical study. The Author(s), 2015 Prostacyclin agonist nationallicence Surgical regeneration therapy nationallicence Drug delivery system nationallicence Translational research nationallicence Preclinical studies nationallicence ANP : Atrial natriuretic peptide nationallicence bFGF : Basic fibroblast growth factor nationallicence BM : Bone marrow nationallicence cAMP : Cyclic adenosine monophostate nationallicence GLP : Good laboratory practice nationallicence HGF : Hepatocyte growth factor nationallicence HUVEC : Human umbilical vein endothelial cell nationallicence LV : Left ventricle nationallicence MI : Myocardial infarction nationallicence NHDF : Normal human dermal fibroblast nationallicence PAH : Pulmonary arterial hypertension nationallicence PLGA : Poly-lactic co-glycolic acid nationallicence SDF : Stromal cell-derived factor nationallicence TGF : Transforming growth factor nationallicence VEGF : Vascular endothelial growth factor nationallicence Fukushima Satsuki Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut Miyagawa Shigeru Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut Sakai Yoshiki Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut Sawa Yoshiki Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut Heart Failure Reviews Springer US; http://www.springer-ny.com 20/4(2015-07-01), 401-413 1382-4147 20:4<401 2015 20 10741 https://doi.org/10.1007/s10741-015-9477-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10741-015-9477-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fukushima Satsuki Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Miyagawa Shigeru Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Sakai Yoshiki Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Sawa Yoshiki Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan aut NATIONALLICENCE 773 0- Heart Failure Reviews Springer US; http://www.springer-ny.com 20/4(2015-07-01), 401-413 1382-4147 20:4<401 2015 20 10741