Development of a System to Obtain Mature Ventricular Cardiomyocytes from Human induced Pluripotent Stem cells

• Project/Area Number: 26713028
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Naito Atsuhiko 東京大学, 医学部附属病院, 助教 (10588891)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000); Fiscal Year 2015: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000); Fiscal Year 2014: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
• Keywords: 細胞・組織 / iPS細胞 / 循環器・高血圧

Outline of Final Research Achievements

Human iPS-derived cardiomyocytes are expected to be useful in cell therapy and drug discovery for heart diseases. In the present study, we developed a novel culture medium and a protocol that enables to cut the cost for cardiomyocyte production to 1/25. We also developed a fluorescence-based, non-genetic method for purifying only ventricular cardiomyocytes.

Research Products

• [Journal Article] iPS細胞を用いた難治性心臓疾患の治療戦略 (2016)
  • Author(s): 伊藤正道、内藤篤彦、小室一成
  • Journal Title: 炎症と免疫 Volume: 24 Pages: 72-76
• [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] iPS細胞を用いた遺伝性心筋疾患の病態解明と治療法開発 (2015)
  • Author(s): 伊藤正道、内藤篤彦、小室一成
  • Journal Title: 日本臨牀増刊号 再生医療 Volume: 73 Pages: 411-415
• [Journal Article] 疾患特異的iPSの臨床2.循環器疾患における現況 (2015)
  • Author(s): 伊藤正道、内藤篤彦、小室一成
  • Journal Title: Surgery Frontier Volume: 22 Pages: 141-145
• [Journal Article] iPS細胞を用いた拡張型心筋症の病態解析 (2015)
  • Author(s): 伊藤正道、内藤篤彦、小室一成
  • Journal Title: 最新医学 Volume: 70 Pages: 107-112
• [Journal Article] Angiotensin II receptor blockade promotes repair of skeletal muscle through down-regulation of aging-promoting C1q expression. (2015)
  • Author(s): Yabumoto C, Akazawa H, Yamamoto R, Yano M, Kudo-Sakamoto Y, Sumida T, Kamo T, Yagi H, Shimizu Y, Saga-Kamo A, Naito AT, Oka T, Lee JK, Suzuki J, Sakata Y, Uejima E, Komuro I.
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 14453-14453
  • DOI: 10.1038/srep14453
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Monocyte-derived extracellular Nampt-dependent biosynthesis of NAD(+) protects the heart against pressure overload. (2015)
  • Author(s): Yano M, Akazawa H, Oka T, Yabumoto C, Kudo-Sakamoto Y, Kamo T, Shimizu Y, Yagi H, Naito AT, Lee JK, Suzuki J, Sakata Y, Komuro I.
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 15857-15857
  • DOI: 10.1038/srep15857
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regeneration of the Cardiac Conduction System by Adipose Tissue-Derived Stem Cells (2015)
  • Author(s): Takahashi T, Nagai T, Kanda M, Liu ML, Kondo N, Naito AT, Ogura T, Nakaya H, Lee JK, Komuro I, Kobayashi Y.
  • Journal Title: Circulation Journal Volume: 79 Issue: 12 Pages: 2703-2712
  • DOI: 10.1253/circj.CJ-15-0400
  • NAID: 130005110933
  • ISSN: 1346-9843, 1347-4820
  • 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] Wnt/β-Catenin Signaling Contributes to Skeletal Myopathy in Heart Failure via Direct Interaction With Forkhead Box O. (2015)
  • Author(s): Okada K, Naito AT, Higo T, Nakagawa A, Shibamoto M, Sakai T, Hashimoto A, Kuramoto Y, Sumida T, Nomura S, Ito M, Yamaguchi T, Oka T, Akazawa H, Lee JK, Morimoto S, Sakata Y, Shiojima I, Komuro I.
  • Journal Title: Circ Heart Fail. Volume: 8 Pages: 799-808
  • Peer Reviewed
• [Journal Article] Complement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling. (2015)
  • Author(s): Sumida T, Naito AT, Nomura S, Nakagawa A, Higo T, Hashimoto A, Okada K, Sakai T, Ito M, Yamaguchi T, Oka T, Akazawa H, Lee JK, Minamino T, Offermanns S, Noda T, Botto M, Kobayashi Y, Morita H, Manabe I, Nagai T, Shiojima I, Komuro I.
  • Journal Title: Nat Commun Volume: 6 Issue: 1 Pages: 6241-6241
  • DOI: 10.1038/ncomms7241
  • Peer Reviewed / Open Access
• [Journal Article] Anti-inflammatory peptides from cardiac progenitors ameliorate dysfunction after myocardial infarction. (2014)
  • Author(s): Liu ML, Nagai T, Tokunaga M, Iwanaga K, Matsuura K, Takahashi T, Kanda M, Kondo N, Naito AT, Komuro I, Kobayashi Y.
  • Journal Title: J Am Heart Assoc Volume: 3 Issue: 6
  • DOI: 10.1161/jaha.114.001101
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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 Issue: 27 Pages: 7839-7850
  • DOI: 10.1016/j.biomaterials.2014.05.080
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Post-myocardial Infarction Remodeling Is Involved in the Progression of Calpain-dependent Cleavage of N-cadherin (2014)
  • Author(s): Yoko Kudo-Sakamoto, Hiroshi Akazawa, Kaoru Ito, Jiro Takano, Masamichi Yano, Chizuru Yabumoto, Atsuhiko T. Naito, Toru Oka, Jong-Kook Lee, Yasushi Sakata, Jun-ichi Suzuki, Takaomi C. Saido and Issei Komuro
  • Journal Title: The journal of biological chemistry Volume: 289 Issue: 28 Pages: 19408-19419
  • DOI: 10.1074/jbc.m114.567206
  • Peer Reviewed
• [Presentation] Drug Discovery against Heart Failure using Human iPS-derived Cardiomyocytes (2016)
  • Author(s): Atsuhiko Naito
  • Organizer: Keystone Symposia Modern Phenotypic Drug Discovery
  • Place of Presentation: Bigsky, Montana
  • Year and Date: 2016-04-04
  • Int'l Joint Research
• [Presentation] Drug Discovery using hiPS-derived Cardiomyocytes (2016)
  • Author(s): Atsuhiko Naito
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-03-19
• [Presentation] iPS細胞由来心筋細胞の創薬への応用 (2015)
  • Author(s): 内藤篤彦
  • Organizer: 第19回日本心不全学会学術集会
  • Place of Presentation: グランフロント大阪（大阪府大阪市）
  • Year and Date: 2015-10-24
  • Invited
• [Presentation] 幹細胞由来心筋細胞の医学研究への応用 (2015)
  • Author(s): 内藤篤彦
  • Organizer: 第5回レギュラトリーサイエンス学会学術集会
  • Place of Presentation: 一橋大学一橋講堂（東京都千代田区）
  • Year and Date: 2015-09-02
  • Invited
• [Presentation] ヒトiPS細胞の創薬への応用 (2015)
  • Author(s): 内藤篤彦
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-04-25
• [Presentation] Wntシグナルと心臓の生老病死 (2014)
  • Author(s): 内藤 篤彦
  • Organizer: 脳心血管抗加齢研究会2014
  • Place of Presentation: 大阪
  • Year and Date: 2014-12-07
  • Invited
• [Presentation] Scalable, reproducible, and echonomical method for producing cardiomyocytes from human iPS cells. (2014)
  • Author(s): Masamichi Ito, Ryoko Takizawa, Natsumi Igarashi, Megumi Naito, Issei Komuro, and Atsuhiko Naito
  • Organizer: American Heart Association Scientific Sessions 2014
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-11-16 – 2014-11-18
• [Presentation] iPS細胞を用いた循環器疾患に対する創薬 (2014)
  • Author(s): 内藤 篤彦
  • Organizer: For the Better Forum 2014
  • Place of Presentation: 東京
  • Year and Date: 2014-11-12
  • Invited
• [Presentation] Wntシグナルと心臓の生老病死 (2014)
  • Author(s): 内藤 篤彦
  • Organizer: 第６６回日本皮膚科学会西部支部学術集会
  • Place of Presentation: 高松
  • Year and Date: 2014-11-09
  • Invited
• [Presentation] Non-genetic method for purification of ventricular cells from human iPS-derived cardiomyocytes. (2014)
  • Author(s): Yuki Kuramoto, Masamichi Ito, and Atsuhiko Naito
  • Organizer: Safety Pharmacology Society Annual Meeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-10-19 – 2014-10-22
• [Presentation] Scalable, reproducible, and echonomical method for producing cardiomyocytes from human iPS cells. (2014)
  • Author(s): Masamichi Ito, Yuki Kuramoto, and Atsuhiko Naito
  • Organizer: Safety Pharmacology Society Annual Meeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-10-19 – 2014-10-22
• [Presentation] Drug Discovery Against Heart Failure using Human iPS cells. (2014)
  • Author(s): 内藤 篤彦
  • Organizer: 第18回日本心不全学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-10
  • Invited
• [Presentation] 2.Tomoaki Higo, Atsuhiko Naito, Yasushi Sakata, and Issei Komuro: Pathogenic role of DNA single strand break accumulation in heart failure. (2014)
  • Author(s): Tomoaki Higo, Atsuhiko Naito, Yasushi Sakata, and Issei Komuro
  • Organizer: Basic Cardiovascular Sciences Scientific Sessions
  • Place of Presentation: Las Vegas, USA
  • Year and Date: 2014-07-14 – 2014-07-17
• [Presentation] Activation of canonical Wnt signaling in arterial endothelial cell induces cardiac dysfunction. (2014)
  • Author(s): Akito Nakagawa, Atsuhiko Naito, Tomokazu Sumida, Seitaro Nomura, Masato Shibamoto, Tomoaki Higo, Katsuki Okada, and Issei Komuro
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: Kyoto
  • Year and Date: 2014-04-14 – 2014-04-17
• [Remarks]
  • URL: http://www.ips-heart.com
• [Patent(Industrial Property Rights)] 心筋細胞の製造方法、心室型心筋細胞及びその製造方法、並びにスクリーニング方法 (2014)
  • Inventor(s): 内藤篤彦、小室一成
  • Industrial Property Rights Holder: 内藤篤彦、小室一成
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-208147
  • Filing Date: 2014-10-09
• [Patent(Industrial Property Rights)] 多能性幹細胞から心筋細胞を分化誘導する方法、並びに該方法に好適な培地添加剤、分化誘導調節剤、培地、培地作製用キット、及び多能性幹細胞から心筋細胞を分化誘導するためのキット (2014)
  • Inventor(s): 内藤篤彦
  • Industrial Property Rights Holder: 内藤篤彦
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-178285
  • Filing Date: 2014-09-02