Research for treatment of refractory arrhythmia with induced-pluripotent stem cells-derived cardiomyocytes

• Project/Area Number: 25505004
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Regenerative medicine
• Research Institution: Keio University
• Principal Investigator: Jun Fujita 慶應義塾大学, 医学部, 講師 (10306706)
• Co-Investigator(Renkei-kenkyūsha): FUKUDA Keiichi 慶應義塾大学, 医学部, 教授 (20199227)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 再生医療 / iPS細胞 / 再生心筋細胞 / 不整脈治療 / 不整脈 / ペースメーカー細胞 / HCN4 / 心筋細胞分化 / 細胞移植療法 / CRISPR/Cas9 / TALEN / CRISPR

Outline of Final Research Achievements

In order to advance the cell therapy for cardiac arrhythmia, massive amount of iPS Cells-derived cardiomyocytes are necessary. Therefor the massive suspension culture system with a spinner flask and efficient purification strategy of cardiomyocytes were invented. Artificial nucleases were used to insert the fluorescent proteins into the specific locus of cardiac-specific transcription factor (NKX2-5) and conduction system specific gene. These cell lines were specifically differentiated and analyzed. Purified cardiomyocytes were transplanted into pigs and the transplantation strategy was evaluated. Cardiac telemetry transmitters were also implanted into pigs and the evaluation system of arrhythmia was established.

Research Products

• [Journal Article] Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells. (2016)
  • Author(s): Tohyama S, Fujita J, Hishiki T, Matsuura T, Hattori F, Ohno R, Kanazawa H, Seki T, Nakajima K, Kishino Y, Okada M, Hirano A, Kuroda T, Yasuda S, Sato Y, Yuasa S, Sano M, Suematsu M, Fukuda K.
  • Journal Title: Cell Metab Volume: 23 Issue: 4 Pages: 663-74
  • DOI: 10.1016/j.cmet.2016.03.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A massive suspension culture system with metabolic purification for human pluripotent stem cell-derived cardiomyocytes. (2014)
  • Author(s): Hemmi N**, Tohyama S**, Nakajima K, Kanazawa H, Suzuki T, Hattori F, Seki T, Kishino Y, Hirano A, Okada M, Tabei R, Ohno R, Fujita C, Haruna T, Yuasa S, Sano M, Fujita J, Fukuda K.
  • Journal Title: Stem Cells Translational Medicine Volume: ３ Issue: 12 Pages: 1473-83
  • DOI: 10.5966/sctm.2014-0072
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Future Prospects for Regenerated Heart Using Induced Pluripotent Stem Cells (2014)
  • Author(s): Fujita J, Fukuda K
  • Journal Title: Journal of Pharmacological Sciences Volume: 125 Issue: 1 Pages: 1-5
  • DOI: 10.1254/jphs.14R01CP
  • NAID: 130003391517
  • ISSN: 1347-8613, 1347-8648
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Future Prospects for Regenerated Heart Using Induced Pluripotent Stem Cells (2014)
  • Author(s): Jun Fujita, and Keiichi Fukuda
  • Journal Title: Journal of Pharmacological Sciences Volume: 印刷中
  • NAID: 130003391517
  • Peer Reviewed
• [Presentation] 心臓再生への挑戦 (2015)
  • Author(s): 藤田淳
  • Organizer: 慶應大学医工薬コモンズ 第10回インキュベーションラウンジ
  • Place of Presentation: 慶應義塾大学理工学部(神奈川県横浜市)
  • Year and Date: 2015-12-16
  • Invited
• [Presentation] Generation of NKX2-5 DsRed/w hiPSCs using TALE nucleases. (2015)
  • Author(s): 大野 麗、遠山 周吾、藤田 淳、福田 恵一
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県神戸市)
  • Year and Date: 2015-12-01
• [Presentation] 心臓再生医療への挑戦 (2015)
  • Author(s): 藤田淳
  • Organizer: 新・CPC運用支援セミナー「これでいいの!?バリデーション・ベリフィケーション」
  • Place of Presentation: メルパルク大阪(大阪府大阪市)
  • Year and Date: 2015-10-28
  • Invited
• [Presentation] iPS細胞を用いた心筋再生医療 (2015)
  • Author(s): 藤田淳
  • Organizer: 第２回富山大学臓器再生カンファレンス2015
  • Place of Presentation: 富山大学工学部(富山県富山市)
  • Year and Date: 2015-07-21
  • Invited
• [Presentation] iPS細胞を用いた心臓再生医療における課題の克服に向けて (2015)
  • Author(s): 藤田淳
  • Organizer: 第14回日本再生医療学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2015-03-19 – 2015-03-21
  • Invited
• [Presentation] 代謝的アプローチによるヒトES/iPS細胞を用いた心臓再生医療 (2015)
  • Author(s): 遠山周吾、藤田淳、服部文幸、菱木貴子、末松誠、福田恵一
  • Organizer: 第14回日本再生医療学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2015-03-19 – 2015-03-21
  • Invited
• [Presentation] A Massive Suspension Culture System With Metabolic Purification for Human Pluripotent Stem Cell-Derived Cardiomyocytes (2015)
  • Author(s): 邉見奈津子、遠山周吾、中嶋一晶、平野暁教、金澤英明、関倫久、岸野喜一、岡田麻里奈、田部井亮太、大野麗、藤田千花、山口美穂、服部文幸、湯浅慎介、佐野元昭、藤田淳、福田恵一
  • Organizer: 第14回日本再生医療学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2015-03-19 – 2015-03-21
• [Presentation] 代謝的アプローチによるヒトES/iPS細胞を用いた心臓再生医療 (2015)
  • Author(s): 遠山周吾、藤田淳、逸見奈津子、服部文幸、福田恵一
  • Organizer: 第18回武田科学振興財団生命科学シンポジウム
  • Place of Presentation: 武田薬品研修所
  • Year and Date: 2015-01-15 – 2015-01-17
• [Presentation] iPS細胞を用いた心不全治療の現状と展望 (2014)
  • Author(s): 藤田淳
  • Organizer: 第３回実験動物科学
  • Place of Presentation: 山形テルサアプローズ
  • Year and Date: 2014-12-12
  • Invited
• [Presentation] 多能性幹細胞の代謝と心臓再生医療 (2014)
  • Author(s): 遠山周吾、藤田淳、服部文幸、菱木貴子、末松誠、福田恵一
  • Organizer: 第18回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 横浜市開港記念会館
  • Year and Date: 2014-11-21
  • Invited
• [Presentation] Clinical Application of Induced Pluripotent Stem Cells for Heart Failure Treatment: Potentials, Progress, and Obstacles (2014)
  • Author(s): Jun Fujita
  • Organizer: American Heart Association. Scientific Sessions 2014 AHA-JCS Joint Symposium
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-11-15 – 2014-11-19
  • Invited
• [Presentation] Current perspectives on cardiac regenerative therapy with human induced pluripotent stem cells (2014)
  • Author(s): 藤田淳
  • Organizer: 第18回心不全学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-10-10 – 2014-10-12
  • Invited
• [Presentation] iPS細胞を用いた心筋再生医療の現状と展望 (2014)
  • Author(s): 藤田淳
  • Organizer: 2014年度 富山大学 生命融合科学教育部大学院特別講義
  • Place of Presentation: 富山大学
  • Year and Date: 2014-06-24
  • Invited
• [Presentation] A Massive Floating Culture System with Metabolic Purification for Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (2014)
  • Author(s): Natsuko Hemmi, Shugo Tohyama, Kazuaki Nakajima, Akinori Hirano, Hideaki Kanazawa, Seki Tomohisa, Yoshikazu Kishino, Marina Okada, Ryota Tabei, Rei Ohno, Chihana Fujita, Miho Yamaguchi, Fumiyuki Hattori, Shinsuke Yuasa, Motoaki Sano, Jun Fujita, Keiichi Fukuda
  • Organizer: International society for stem cell research, 12th annual meeting 2014
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2014-06-18 – 2014-06-21
• [Presentation] iPS細胞を用いた心筋再生医療の現状と展望 (2014)
  • Author(s): 藤田淳
  • Organizer: 第13回再生医療学会
  • Place of Presentation: 京都国際会館
  • Invited
• [Presentation] A massive floating culture system with metabolic purification for human induced pluripotent stem cell-derived cardiomyocytes (2014)
  • Author(s): Hemmi Natsuko, Tohyama Shugo, Nakajima Kazuaki, Hirano Akinori, Kanazawa Hideaki, Seki Tomohisa, Kishino Yoshikazu, Okada Marina, Tabei Ryota, Ohno Rei, Fujita Chihana, Yamaguchi Miho, Hattori Fumiyuki, Yuasa Shinsuke, Sano Motoaki, Fujita Jun, Fukuda Keiichi
  • Organizer: International society for stem cell research, 12th annual meeting
  • Place of Presentation: Vancouver
• [Presentation] Heart - a Regenerated Cardiomyocyte Transplantation method using Human ES/iPS Cells: Creation of Hearts using iPS/ ES cells (2013)
  • Author(s): Jun Fujita
  • Organizer: 12th Congress of the International Xenotransplantation Association (IXA)
  • Place of Presentation: Osaka
  • Invited
• [Presentation] マイクロミニブタにおける移植細胞同定のためのAcGFP陽性ヒトiPS細胞の作製 (2013)
  • Author(s): 大野 麗, 遠山 周吾, 平野 暁教, 辺見 奈津子, 中嶋 一晶, 金澤 英明, 寺谷 工, 小林 英司, 藤田 淳, 福田 恵一
  • Organizer: 分子生物学会
  • Place of Presentation: 神戸ポートアイランド
• [Book] BIO Clinica；心筋再生医療の現状と展望 (2015)
  • Author(s): 藤田淳
  • Total Pages: 4
  • Publisher: 北隆館
• [Book] 医学のあゆみ；iPS細胞をも引いた心臓再生医療の現状と課題 (2014)
  • Author(s): 藤田淳、福田恵一
  • Total Pages: 6
  • Publisher: 医歯薬出版株式会社