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A therapeutic angiogenesis of sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel sheets in a canine chronic myocardial infarction model

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Abstract

This study investigated the safety and efficacy of a sustained release of basic fibroblast growth factor (bFGF) with biodegradable gelatin hydrogel sheets as therapeutic angiogenesis in canine chronic myocardial infarction (MI) models. Canine chronic MI model was induced by ligating the left anterior descending coronary artery and its diagonal branches. At 4 week post-induction, we applied either saline (Control group, n = 5) or 200 μg of bFGF (Treatment group, n = 6) soaked gelatin hydrogel sheets on the ischemic area of the left ventricular (LV) wall. At 6 weeks after the procedure, we evaluated the efficacy by echocardiography and immunohistochemical study. There were no procedure-related adverse events or deaths. The serum bFGF level was under detectable levels in all animals at any sampling points. In terms of efficacy, echocardiographic evaluation demonstrated that fractional shortening was significantly improved in the treatment group. In addition, immunohistochemical study showed that the capillary density in the border zone of the MI area, as well as the MI area, significantly increased in the treatment group. Therapeutic angiogenesis by bFGF using biodegradable gelatin hydrogel sheets was safe, increased the capillary density, and improved LV function in canine chronic MI models.

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Acknowledgements

This work was supported by research grants from the Ministry of Health, Labor and Welfare, Japan [Grant no. 201409024A] (to R.S.) and Invited Research Project of Translational Research Center, Kyoto University Hospital (to R.S.). We thank Dr. Hemant Poudyal (Kyoto University) for the critical reading of the manuscript.

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Author notes

  1. Motoyuki Kumagai

    Present address: Department of Cardiovascular Surgery, Hamamatsu Rosai Hospital, Hamamatsu, Japan

  2. Kenji Minakata

    Present address: Division of Cardiovascular Surgery, Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA

  3. Masaya Yamamoto

    Present address: Department of Materials Processing, Graduate School of Engineering, Tohoku University, Sendai, Japan

  4. Kyokun Uehara

    Present address: Department of Cardiovascular Surgery, National Cerebral and Cardiovascular Center, Osaka, Japan

  5. Ryuzo Sakata

    Present address: Department of Cardiovascular Surgery, Osaka Red Cross Hospital, Osaka, Japan

Authors and Affiliations

  1. Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Motoyuki Kumagai, Kenji Minakata, Hidetoshi Masumoto, Kyokun Uehara, Kazuhiro Yamazaki, Tadashi Ikeda, Ryuzo Sakata & Kenji Minatoya

  2. Department of Biomaterials, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan

    Masaya Yamamoto & Yasuhiko Tabata

  3. Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan

    Atsushi Yonezawa & Kazuo Matsubara

  4. Department of Experimental Therapeutics, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan

    Takafumi Ikeda & Akira Shimizu

  5. Department of Clinical Innovative Medicine Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan

    Masayuki Yokode

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  1. Motoyuki Kumagai
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Correspondence to Hidetoshi Masumoto.

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Kumagai, M., Minakata, K., Masumoto, H. et al. A therapeutic angiogenesis of sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel sheets in a canine chronic myocardial infarction model. Heart Vessels 33, 1251–1257 (2018). https://doi.org/10.1007/s00380-018-1185-6

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  • DOI: https://doi.org/10.1007/s00380-018-1185-6

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