Development of new treatment of heart failure using induced pluripotent stem cells-derived cardiomyocytes

• Project/Area Number: 23659669
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Thoracic surgery
• Research Institution: Osaka University
• Principal Investigator: NISHI Hiroyuki 大阪大学, 医学系研究科, 助教 (00529208)
• Co-Investigator(Kenkyū-buntansha): SAWA Yoshiki 大阪大学, 大学院・医学系研究科, 教授 (00243220) ; 倉谷 徹 大阪大学, 大学院・医学系研究科, 寄附講座教授 (90448035) ; 宮川 繁 大阪大学, 大学院・医学系研究科, 講師 (70544237) ; 吉川 泰司 大阪大学, 大学院・医学系研究科, 助教 (40570594) ; 福嶌 五月 大阪大学, 大学院・医学系研究科, 助教 (80596867)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: iPS 細胞 / 心筋細胞シート / 心筋梗塞 / 心不全 / iPS細胞

Research Abstract

Induced pluripotent stem cells (iPS cells) of human origin were cultivated and differentiated to cardiomyocytes by originally developed protocol. Cardiomyocyte cell-sheet was then generated from the cardiomyocytes derived from the iPS cells. Transplantation of cardiomyocyte cell-sheets into the infarct heart induced functional integration of the iPS cells-derived cardiomyocytes into the cardiac tissue, contributing to functional recovery, in a rat and a porcine model.

Research Products

• [Journal Article] In vivo differentiation of induced pluripotent stem cell-derived cardiomyocytes (2013)
  • Author(s): Yu T, Miyagawa S, Miki K, Saito A, Fukushima S, Higuchi T, Kawamura M, Kawamura T, Ito E, Kawaguchi N, Sawa Y, Matsuura N
  • Journal Title: Circ J. Volume: 77(5) Pages: 1297-306
  • NAID: 10031151394
  • URL: http://dx.doi.org/10.1253/circj.CJ-12-0977
  • Peer Reviewed
• [Journal Article] In Vivo Differentiation of Induced Pluripotent Stem Cell-Derived Cardiomyocytes (2013)
  • Author(s): Yu T.
  • Journal Title: Circulation Journal Volume: 77 Issue: 5 Pages: 1297-1306
  • DOI: 10.1253/circj.CJ-12-0977
  • NAID: 10031151394
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Bioengineered myocardium derived from induced pluripotent stem cells improves cardiac function and attenuates cardiac remodeling following chronic myocardial infarction in rats (2012)
  • Author(s): Miki K, Uenaka H, Saito A, Miyagawa S, Sakaguchi T, Higuchi T, Shimizu T, Okano T, Yamanaka S, Sawa Y.
  • Journal Title: Stem Cells Translational Medicine Volume: 1 Issue: 5 Pages: 430-437
  • DOI: 10.5966/sctm.2011-0038
  • Peer Reviewed
• [Journal Article] Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. (2012)
  • Author(s): Kawamura M, Miyagawa S, Miki K, Saito A, Fukushima S, Higuchi T, Kawamura T, Kuratani T, Daimon T, Shimizu T, Okano T, Sawa Y.
  • Journal Title: Circulation Volume: 11;126(11 Suppl 1) Issue: 11_suppl_1
  • DOI: 10.1161/circulationaha.111.084343
  • Peer Reviewed
• [Journal Article] Induced adipocyte cell-sheet ameliorates cardiac dysfunction in a mouse myocardial infarction model: a novel drug delivery system for heart failure. (2011)
  • Author(s): Imanishi Y, Sawa Y(7)
  • Journal Title: Circulation. Volume: 3;124(11 Suppl)
  • Peer Reviewed
• [Journal Article] Novel regenerative therapy using cell-sheet covered with omentum flap delivers a huge number of cells in a porcine myocardial infarction model. (2011)
  • Author(s): Shudo Y, Sawa Y(11).
  • Journal Title: J Thorac Cardiovasc Surg. Volume: 142（5） Pages: 1188-96
  • Peer Reviewed
• [Journal Article] Clinical impact of combined transplantation of autologous skeletal myoblasts and bone marrow mononuclear cells in patients with severely deteriorated ischemic cardiomyopathy. (2011)
  • Author(s): Fujita T, Sawa Y(7).
  • Journal Title: Surg Today. Volume: 41(8) Pages: 1029-36
  • NAID: 10029284004
  • Peer Reviewed
• [Journal Article] Allogenic skeletal myoblast transplantation in acute myocardial infarction model rats. (2011)
  • Author(s): Imanishi Y, Miyagawa S(2), Saito A(3), Sawa Y(5).
  • Journal Title: Transplantation. Volume: 91(4) Pages: 425-31
  • Peer Reviewed
• [Journal Article] Tissue-engineered cardiac constructs for cardiac repair. (2011)
  • Author(s): Miyagawa S, Sawa Y(3).
  • Journal Title: Ann Thorac Surg. Volume: 91(1) Pages: 320-9
  • Peer Reviewed
• [Presentation] Development of Vascular-Rich Tissue Containing Cardiomyocytes Derived from Human iPS Cells in vivo. (2012)
  • Author(s): Masashi Kawamura
  • Organizer: American Heart Association Scientific Meeting 2012
  • Place of Presentation: ロサンゼルス・コンベンションセンター.米国
• [Presentation] iPS細胞由来心筋前駆細胞シートによる 重症心不全治療の縦断的開発. (2012)
  • Author(s): 福嶌五月
  • Organizer: 第11回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] ミニブタ虚血性心筋症モデルに対するヒト iPS 細胞由来心筋細胞シートの治療効果の検討 (2012)
  • Author(s): 川村 匡
  • Organizer: 第11回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] ミニブタ虚血性心筋症モデルに対するヒトiPS細胞由来心筋細胞シートの治療効果の検討 (2012)
  • Author(s): 川村 匡
  • Organizer: 第11回日本再生医療学会
  • Place of Presentation: 横浜
• [Presentation] iPS細胞由来心筋前駆細胞シートによる 重症心不全治療の縦断的開発 (2012)
  • Author(s): 福嶌五月
  • Organizer: 第11回日本再生医療学会
  • Place of Presentation: 横浜
• [Presentation] Development of Vascular-Rich Tissue Containing Cardiomyocytes Derived from Human iPS Cells in vivo (2012)
  • Author(s): Kawamura M
  • Organizer: America Heart Association 2012
  • Place of Presentation: Los Angeles
• [Presentation] In Vivo Functional Evaluation of Induced Pluripotent Stem Cell-Derived Cardiomyocytes Implanted into the Rat Chronic Infarction Model. (2011)
  • Author(s): Takahiro Higuchi
  • Organizer: American Heart Association Scientific Meeting 2011
  • Place of Presentation: オーランドコンベンションセンター 米国
• [Presentation] Tissue-Engineerd Cell Sheets to Facilitate VAD Wean. (2011)
  • Author(s): Sawa Y.
  • Organizer: 49th American Heart Association (AHA)
  • Place of Presentation: Orland,USA
• [Presentation] Combined Therapy of Skeletal Myoblast Cell-Sheet Transplantation with Administration of Prostacycline Agonist Makes Left Ventricular Reverse Remodeling on the Impaired Myocardium in Rapid-Pacing Induced End-stage Heart Failure in Canine Heart (2011)
  • Author(s): Shirasaka T.
  • Organizer: 49th American Heart Association (AHA)
  • Place of Presentation: Orland,USA
• [Presentation] Myoblast Sheet Implantation Can Prevent the Impairment of Cardiac Diastolic Function after Left Ventricular Restoration by Modulating the Extracellular Matrix Gene Expression. (2011)
  • Author(s): Saito S, Sakaguchi T, Miyagawa S, Nishi H, Yoshikawa Y, Fukushima S, Ueno T, Kuratani T, Saito A, Sawa Y.
  • Organizer: Progress Meeting on International consortium for cardiac tissue engineering Tampere
  • Place of Presentation: Tampere,Finland
• [Presentation] Novel Regenerative Therpy Using Cell-Sheet Covered with Omentum Flap to Deliver Huge Numbers of Cells in a Porcine Myocardial Infarction Model. (2011)
  • Author(s): Shudo Y, Miyaigawa S, Saito A, Sakaguchi T, Kainmuma S, Kuratani T, Sawa Y.
  • Organizer: 91th AATS (American Association for Thoracic Surgery)
  • Place of Presentation: Philadelphia,USA
• [Presentation] Myoblast Sheet Implantation Can Prevent the Impairment of Cardiac Diastolic Function after Left Ventricular Restoration by Modulating the Extracellular Matrix Gene Expression. (2011)
  • Author(s): Saito S, Sakaguchi T, Miyagawa S, Nishi H, Yoshikawa Y, Fukushima S, Ueno T, Kuratani T, Saito A, Sawa Y.
  • Organizer: 31th International Society for Heart and Lung Transplantation
  • Place of Presentation: San Diego,USA