Engineeing of the heart tissues using decellularized extracellular matrix - Development of basic technology to construct three-dimensional organ-like tissues

• Project/Area Number: 26293188
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Osaka University
• Principal Investigator: LEE JONG-KOOK 大阪大学, 医学(系)研究科(研究院), 特任准教授(常勤) (60303608)
• Co-Investigator(Kenkyū-buntansha): 宮川 繁 大阪大学, 医学(系)研究科(研究院), 特任准教授(常勤) (70544237)
• Research Collaborator: MIWA Keiko 大阪大学, 医学系研究科, 特任助教(常勤) ; YOKOYAMA Teruki 大阪大学, 医学系研究科, 大学院生 ; TOMOYAMA Satoki 大阪大学, 医学系研究科, 大学院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2014: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
• Keywords: ３次元組織構築 / 脱細胞化 / 細胞外マトリックス / 心筋細胞 / iPS細胞 / 光学マッピング / 興奮伝播 / 組織透明化 / 脱細胞化心臓マトリックス / 細胞接着因子 / 組織透明化技術 / 再生医学 / 組織工学 / 脱細胞化マトリックス / 臓器構築 / 3次元心筋組織 / 移植

Outline of Final Research Achievements

Adult rat hearts were decellularized with the perfusion of detergents, and then extracellular matrices were recellularized with cardiac cells from neonatal rats. We evaluated functional and morphological properties of organ-like three dimensional heart tissues using optical mapping and other methods. The results were published in an international journal of biomaterial sciences（Yasui et al. Biomaterials. 2014; IF 8.387）. Furthermore, we succeeded in observing coronary vessels and sympathetic nerves of entire murine hearts using tissue-clearing techniques. The technique can be utilized to evaluate detailed morphological properties of organ-like three-dimensional heart tissues. (Yokoyama et al. Presented in AHA2016 etc. The manuscript is in review.)

Research Products

• [Journal Article] Activation of endothelial β-catenin signaling induces heart failure. (2016)
  • Author(s): Nakagawa A, Naito AT, Sumida T, Nomura S, Shibamoto M, Higo T, Okada K, Sakai T, Hashimoto A, Kuramoto Y, Oka T, Lee JK, Harada M, Ueda K, Shiojima I, Limbourg FP, Adams RH, Noda T, Sakata Y, Akazawa H, Komuro I.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 25009-25009
  • DOI: 10.1038/srep25009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A New In Vitro Co-Culture Model Using Magnetic Force-Based Nanotechnology. (2016)
  • Author(s): Takanari H, Miwa K, Fu X, Nakai J, Ito A, Ino K, Honda H, Tonomura W, Konishi S, Opthof T, van der Heyden MA, Kodama I, Lee JK.
  • Journal Title: Journal of Cellular Physiology Volume: 未定 Issue: 10 Pages: 1-8
  • DOI: 10.1002/jcp.25342
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Generation of Induced Pluripotent Stem Cells From Patients With Duchenne Muscular Dystrophy and Their Induction to Cardiomyocytes (2016)
  • Author(s): Hashimoto A, Naito AT, Lee JK, Kitazume-Taneike R, Ito M, Yamaguchi T, Nakata R, Sumida T, Okada K, Nakagawa A, Higo T, Kuramoto Y, Sakai T, Tominaga K, Okinaga T, Kogaki S, Ozono K, Miyagawa S, Sawa Y, Sakata Y, Morita H, Umezawa A, Komuro I.
  • Journal Title: International Heart Journal Volume: 57 Issue: 1 Pages: 112-117
  • DOI: 10.1536/ihj.15-376
  • NAID: 130005120987
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed / Open Access
• [Journal Article] Centrifugal microfluidic platform for single-cell level cardiomyocyte-based drug profiling and screening (2015)
  • Author(s): Espulgar W, Aoki W, Ikeuchi T, Mita D, Saito M, Lee JK, Tamiya E
  • Journal Title: Lab on a Chip Volume: 15 Issue: 17 Pages: 3572-3580
  • DOI: 10.1039/c5lc00652j
  • Peer Reviewed
• [Journal Article] Optical microscopy imaging for the diagnosis of the pharmacological reaction of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) (2015)
  • Author(s): Ikeuchi T, Espulgar W, Shimizu E, Saito M, Lee JK, Dou X, Yamaguchi Y, Tamiya E.
  • Journal Title: Analyst Volume: 140 Issue: 19 Pages: 6500-6507
  • DOI: 10.1039/c5an01144b
  • Peer Reviewed
• [Journal Article] Pirfenidone exhibits cardioprotective effects by regulating myocardial fibrosis and vascular permeability in pressure overloaded hearts. (2015)
  • Author(s): Yamagami K, Oka T, Wang Q, et al.
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 309 Issue: 3 Pages: 512-522
  • DOI: 10.1152/ajpheart.00137.2015
  • Peer Reviewed
• [Journal Article] Excitation propagation in three-dimensional engineered hearts using decellularized extracellular matrix. (2014)
  • Author(s): Yasui H, Lee JK, Yoshida A, Yokoyama T, Nakanishi H, Miwa K, Naito AT, Oka T, Akazawa H, Nakai J, Miyagawa S, Sawa Y, Sakata Y, Komuro I
  • Journal Title: Biomaterials. Volume: 35 Pages: 7839-7850
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] N-glycans: phenotypic homology and structural differences between myocardial cells and induced pluripotent stem cell-derived cardiomyocytes. (2014)
  • Author(s): Kawamura T, Miyagawa S, Fukushima S, Yoshida A, Kashiyama N, Kawamura A, Ito E, Saito A, Maeda A, Eguchi H, Toda K, Lee JK, Miyagawa S, Sawa Y
  • Journal Title: PLoS One Volume: 9 Issue: 10 Pages: e111064-e111064
  • DOI: 10.1371/journal.pone.0111064
  • Peer Reviewed / Open Access
• [Presentation] Three dimensional Architecture of the Cardiac Sympathetic Nervous System in Tissue-Cleared Hearts of Mice of after Myocardial Infarction. (2017)
  • Author(s): Yokoyama T, Lee JK, Miwa K, Miyagawa S, Sawa Y, Sakata Y, Komuro I.
  • Organizer: Gordon Research Seminar 2017.
  • Place of Presentation: Ventura, CA, USA
  • Year and Date: 2017-02-15
  • Int'l Joint Research
• [Presentation] In Vitro Model of Allogenic Cell Transplantation for Conduction Defects - Electrical Coupling Between Rat iPS Cell-Derived Cardiac Cells and Rat Native Cardiac Cells. (2016)
  • Author(s): Yoshida A, Lee JK, Miyagawa S, Sawa Y, Sakata Y.
  • Organizer: AHA 2016 Scieintific Sessions.
  • Place of Presentation: New Orleans, LA , USA
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] Tissue Clearance Technique Enables to Investigate Three-Dimensional Distribution of Cardiac Sympathetic Nervous System. (2016)
  • Author(s): Yokoyama T, Lee JK, Miwa K, Tomoyama S, Nakanishi H, Yoshida A, Miyagawa S, Sawa Y, SakataY.
  • Organizer: AHA 2016 Scientific Sessions
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2016-11-14
  • Int'l Joint Research
• [Presentation] Electrical prperties of stem-cell derived cardiac tissues experimental platforms for research and development. (2016)
  • Author(s): Lee JK
  • Organizer: 1st BioSensing Technology Workshop & Conference 2016
  • Place of Presentation: Manila, Philippine
  • Year and Date: 2016-09-21
  • Int'l Joint Research / Invited
• [Presentation] Autonomic innervation to engineered cardiac tissues- Implication to Biological Pacemaker (2015)
  • Author(s): 李 鍾國
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2015-04-24
  • Invited
• [Presentation] Electrical properties of threedimensional engineered hearts using decellularized extracellular matrix. (2015)
  • Author(s): LeeJ, Yasui H, Yokoyama T, Nakanishi H, Yoshida A, Miwa K, Nakai J, Miyagawa S, Sawa Y, Sakata Y, Komuro I.
  • Organizer: Gordon Research Conference: Cardiac Arrhythmia Mechanisms.
  • Place of Presentation: Garba, Italy
  • Year and Date: 2015-03-22 – 2015-03-27