Development of therapeutic method for heart failure through cellular phenotype control using susutained release of microRNA

• Project/Area Number: 25462136
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Kyoto University
• Principal Investigator: Yamazaki Kazuhiro 京都大学, 医学(系)研究科(研究院), 助教 (50464227)
• Co-Investigator(Kenkyū-buntansha): ONO KOH 京都大学, 大学院医学研究科, 准教授 (00359275) ; SAKATA RYUZO 京都大学, 大学院医学研究科, 名誉教授 (20325781) ; TABATA YASUHIKO 京都大学, 再生医科学研究所, 教授 (50211371) ; 丸井 晃 京都大学, 医学(系)研究科(研究院), その他 (60402856)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 心筋疾患外科学 / 心筋リモデリング / 心不全 / 血管新生 / 心筋モデリング / マイクロＲＮＡ

Outline of Final Research Achievements

We performed the evaluation for optimal mixture condition of gelatin hydrogel and miR-29b using COS-7 cells. We could found the condition to efficiently induce miR-29b complementary plasmid within COS-7, providing suitable condition of better microRNA induction using sustained-release vehicles.
We next evaluated the efficiency of transduction of miR-126-incorporated poly(lactic-co-glycolic acid)(PLGA) for mice hindlimb ischemia model. Treatment with miR-126-incorporated PLGA led to increased blood flow and activation of signaling pathway related to miR-126 in gene and protein expression level. We showed fair efficiency of transduction of microRNA into the target cells which provides a basic knowledge for sustained release of microRNA into the heart muscle tissue.

Research Products

• [Journal Article] Green Tea Polyphenol Prevents Diabetic Rats From Acute Kidney Injury After Cardiopulmonary Bypass. (2016)
  • Author(s): Funamoto M, Masumoto H, Takaori K, Taki T, Setozaki S, Yamazaki K, Minakata K, Ikeda T, Hyon SH, Sakata R.
  • Journal Title: Ann Thorac Surg Volume: 101 Issue: 4 Pages: 1507-13
  • DOI: 10.1016/j.athoracsur.2015.09.080
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia. (2016)
  • Author(s): Kumagai M, Marui A, Tabata Y, Takeda T, Yamamoto M, Yonezawa A, Tanaka S, Yanagi S, Ito-Ihara T, Ikeda T, Murayama T, Teramukai S, Katsura T, Matsubara K, Kawakami K, Yokode M, Shimizu A, Sakata R.
  • Journal Title: Heart Vessels. Volume: 未定
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Efficient long-term survival of cell grafts after myocardial infarction with thick viable cardiac tissue entirely from pluripotent stem cells. (2015)
  • Author(s): Matsuo T, Masumoto H, Tajima S, Ikuno T, Katayama S, Minakata K, Ikeda T, Yamamizu K, Tabata Y, Sakata R, Yamashita JK.
  • Journal Title: Scientific Reports Volume: 5:16842 Issue: 1 Pages: 1-14
  • DOI: 10.1038/srep16842
  • NAID: 120005753829
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MicroRNAs and Lipoprotein Metabolism (2014)
  • Author(s): Horie T, Ono K, et al
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 21 Issue: 1 Pages: 17-22
  • DOI: 10.5551/jat.20859
  • NAID: 130004845461
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed
• [Journal Article] Myocardial expression level of neural cell adhesion molecule correlates with reduced left ventricular function in human cardiomyopathy. (2014)
  • Author(s): Nagao K, Ono K, et al
  • Journal Title: Circ Heart Fail. Volume: 7 Pages: 351-358
  • Peer Reviewed
• [Journal Article] The effect of serum in culture on RNAi efficacy through modulation of polyplexes size. (2014)
  • Author(s): Zhang W, Tabata Y, et al.
  • Journal Title: Biomaterials. Volume: 35 Issue: 1 Pages: 567-577
  • DOI: 10.1016/j.biomaterials.2013.09.102
  • Peer Reviewed
• [Journal Article] MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice. (2013)
  • Author(s): Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Usami S, Izuhara M, Sowa N, Yahagi N, Shimano H, Matsumura S, Inoue K, Marusawa H, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K
  • Journal Title: Nat Commun. Volume: 4:2883 Issue: 1 Pages: 2883-2883
  • DOI: 10.1038/ncomms3883
  • NAID: 120005349007
  • Peer Reviewed / Open Access
• [Journal Article] Metastasis-associated protein, S100A4 mediates cardiac fibrosis potentially through the modulation of p53 in cardiac fibroblasts (2013)
  • Author(s): Tamaki Y, Iwanaga Y, Niizuma S, Kawashima T, Kato T, Inuzuka Y, Horie T, Morooka H, Takase T, Akahashi Y, Kobuke K, Ono K, Shioi T, Sheikh SP, Ambartsumian N, Lukanidin E, Koshimizu TA, Miyazaki S, Kimura T
  • Journal Title: J Mol Cell Cardiol Volume: 57 Pages: 72-81
  • DOI: 10.1016/j.yjmcc.2013.01.007
  • Peer Reviewed
• [Journal Article] 分子生物学的検討により動脈硬化を診る：HDL-C標的療法としてのマイクロRNA-33の抑制の可能性 (2013)
  • Author(s): 尾野 亘
  • Journal Title: 臨床病理 Volume: 61 Pages: 934-939
• [Journal Article] microRNA-33a/bの制御によるHDLコレステロールレベル制御機構の解明と動脈硬化に対する新規治療法の開発 (2013)
  • Author(s): 尾野 亘
  • Journal Title: 細胞科学 Volume: 24 Pages: 20-27
  • NAID: 40019873043
• [Journal Article] プラークとmicroRNA (2013)
  • Author(s): 尾野 亘
  • Journal Title: カレントテラピー Volume: 31 Pages: 54-59
• [Journal Article] Human RGM249-derived small RNAs potentially regulate tumor malignancy. (2013)
  • Author(s): Miura N, Shimizu M, Shinoda W, Tsuno S, Sato R, Wang X, Jo J, Tabata Y, Hasegawa J.
  • Journal Title: Nucleic Acid Therapeutics Volume: 23(5) Issue: 5 Pages: 332-343
  • DOI: 10.1089/nat.2013.0424
  • Peer Reviewed
• [Presentation] マウス下肢虚血モデルにおけるmicroRNA-126の局所徐放による血管新生効果 (2016)
  • Author(s): 津丸真一、坂田隆造ほか
  • Organizer: 第44回日本血管外科学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2016-05-25
• [Presentation] Therapeutic angiogenesis by local sustained release of microRNA-126 in murine hindlimb ischemia (2016)
  • Author(s): Tsumaru S, Sakata R et al.
  • Organizer: the 24th Annual Meeting of Asian Society for Cardiovascular and Thoracic Surgery (ASCVTS)
  • Place of Presentation: 台北、台湾
  • Year and Date: 2016-04-06
  • Int'l Joint Research
• [Presentation] Therapeutic angiogenesis by local sustained release of microRNA-126 in murine hindlimb ischemia (2016)
  • Author(s): Tsumaru S, Sakata R et al.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台市
  • Year and Date: 2016-03-18
• [Presentation] マウス下肢虚血モデルにおけるmicroRNA-126の局所徐放による血管新生効果 (2016)
  • Author(s): 津丸真一、坂田隆造ほか
  • Organizer: 第46回日本心臓血管外科学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2016-02-15
• [Presentation] 再生医療への科学技術インテグレーション －再生研究と再生治療－ (2014)
  • Author(s): 田畑 泰彦
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] Cardiac-specific inhibition of kinase activity in calcium/calmodulin-dependent kinase kinase- leads to accerelated left ventricular remodeling and heart failure after transverse aortic constriction in mice. (2013)
  • Author(s): Ono K
  • Organizer: Cold spring harbor laboratory meeting.
  • Place of Presentation: NY, U.S.A.
• [Presentation] マイクロRNAのバイオマーカーとしての応用 (2013)
  • Author(s): 尾野亘
  • Organizer: 第45回日本動脈硬化学会
  • Place of Presentation: 京王プラザホテル
• [Presentation] microRNAと動脈硬化・心不全 (2013)
  • Author(s): 尾野亘
  • Organizer: 第23回 循環薬理学会
  • Place of Presentation: 福岡メディカルホール
• [Book] Annual Review循環器：心筋再生医療の進歩 (2016)
  • Author(s): 升本英利、坂田隆造
  • Total Pages: 7
  • Publisher: 中外医学社
• [Remarks] 京都大学 心臓血管外科
• [Remarks] 京都大学 心臓血管外科
  • URL: http://kyoto-cvs.jp/