Three-dimensional reconstruction of bioartificial heart by reprogrammed human cardiomyocytes

• Project/Area Number: 25670389
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Okayama University
• Principal Investigator: OH HIDEMASA 岡山大学, 大学病院, 教授 (50372579)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: バイオ人工心臓 / 心臓内幹細胞 / 細胞外マトリックス / 人工心筋細胞 / 血管内皮細胞 / 脱細胞化 / 再播種

Outline of Final Research Achievements

The shortage of donors for heart transplantation has become a critical issue to treat the patients with end-stage of cardiac failure. We have decellularized the rat whole heart by using pulsatile perfusion apparatus. Reprogrammed human cardiomyocytes were mixed with endothelial progenitor cells in culture and those were perfused to recellularize the acellular construct. Following 8 to 10 days in continuous perfusion, reseeded cells were engrafted onto the matrix to reconstruct the entire vascular beds and myocardium ex vivo.

Research Products

• [Journal Article] Intracoronary Autologous Cardiac Progenitor Cell Transfer in Patients with Hypoplastic Left Heart Syndrome: The TICAP Prospective Phase 1 Controlled Trial. (2015)
  • Author(s): Ishigami S, Ohtsuki S, Tarui S, Ousaka D, Eitoku T, Kondo M, Okuyama M, Kobayashi J, Baba K, Arai S, Kawabata T, Yoshizumi K, Tateishi A, Kuroko Y, Iwasaki T, Sato S, Kasahara S, Sano S, Oh H.
  • Journal Title: Circulation Research Volume: 116 Issue: 4 Pages: 653-664
  • DOI: 10.1161/circresaha.116.304671
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Epigenetic modification in congenital heart diseases by using stem cell technologies (2015)
  • Author(s): Kobayashi J., Sano S., Oh H.
  • Journal Title: Stem Cell Epigenetics Volume: 2
  • DOI: 10.14800/sce.550
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors. (2014)
  • Author(s): Ogata T, Naito D, Nakanishi N, Hayashi YK, Taniguchi T, Miyagawa K, Hamaoka T, Maruyama N, Matoba S, Ikeda K, Yamada H, Oh H, Ueyama T.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 111 Issue: 10 Pages: 3811-3816
  • DOI: 10.1073/pnas.1315359111
  • Peer Reviewed / Open Access
• [Journal Article] Stem cell therapy in patients with single ventricle physiology. (2014)
  • Author(s): Tarui S, Sano S, Oh H.
  • Journal Title: Methodist DeBakey Cardiovascular Journal Volume: 10 Pages: 77-81
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Directed Differentiation of Patient-Specific Induced Pluripotent Stem Cells Identifies the Transcriptional Repression and Epigenetic Modification of NKX2-5, HAND1, and NOTCH1 in Hypoplastic Left Heart Syndrome. (2014)
  • Author(s): Kobayashi J., Yoshida M., Tarui S., Hirata M., Nagai Y., Kasahara S., Keiji K., Ito H., Sano S., Oh H.
  • Journal Title: PLOS One Volume: 9 Issue: 7 Pages: e102796-e102796
  • DOI: 10.1371/journal.pone.0102796
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 心筋幹細胞を用いた先天性心疾患に対する心筋再生医療 (2013)
  • Author(s): 樽井俊、佐野俊二、王 英正
  • Journal Title: 月刊循環器 Volume: 3 Pages: 69-76
• [Presentation] 心臓内幹細胞を用いた小児心疾患の解明と再生医療 (2014)
  • Author(s): 王 英正
  • Organizer: 高知小児循環器・川崎病研究会
  • Place of Presentation: 高知
  • Year and Date: 2014-12-04
  • Invited
• [Presentation] 臨床試験における具体的な評価指標の定め方 (2014)
  • Author(s): 王 英正
  • Organizer: 技術情報協会セミナー
  • Place of Presentation: 東京
  • Year and Date: 2014-10-07
  • Invited
• [Presentation] 心臓内幹細胞を用いた小児心疾患の解明と再生医療 (2014)
  • Author(s): 王 英正
  • Organizer: 岡山先端医学研究会
  • Place of Presentation: 岡山
  • Year and Date: 2014-09-26
  • Invited
• [Presentation] 心臓内幹細胞を用いた小児心疾患の解明と再生医療 (2014)
  • Author(s): 王 英正
  • Organizer: 第34回日本小児病理研究会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2014-09-06
  • Invited
• [Presentation] 先天性心疾患への再生医療の現状 (2014)
  • Author(s): 王 英正
  • Organizer: 抗加齢医学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2014-06-06
  • Invited
• [Presentation] 左心低形成症候群に対する心臓内幹細胞を用いた自家移植療法 (2014)
  • Author(s): 樽井俊、佐野俊二、王 英正
  • Organizer: 第13回心血管再生外科治療研究会
  • Place of Presentation: 熊本
• [Presentation] ３D細胞外マトリックスを利用したヒト幹細胞再播種によるバイオ人工心臓の作成 (2014)
  • Author(s): 奥山倫弘，逢坂大樹，石神修大，小林純子，笠原真悟，佐野俊二，王 英正
  • Organizer: 日本再生医療学会
  • Place of Presentation: 京都
• [Presentation] 左心低形成症候群に対する心臓内幹細胞自家移植療法：第1相試験（TICAP） (2014)
  • Author(s): 樽井俊、石神修大、大月審一、逢坂大樹、栄徳隆裕、近藤麻衣子、小林純子、奥山倫弘、馬場健児、川畑拓也、吉積 功、黒子 洋介、新井禎彦、岩崎達雄、佐藤修平、笠原真悟、佐野俊二、王 英正
  • Organizer: 日本再生医療学会
  • Place of Presentation: 京都
• [Presentation] 患者由来iPS細胞を用いた左心低形成症候群における疾患発症機序の解明 (2014)
  • Author(s): 小林純子，吉田 賢司，樽井 俊，永井祐介，笠原真悟，成瀬恵治，伊藤 浩，佐野俊二，王 英正
  • Organizer: 日本再生医療学会
  • Place of Presentation: 京都
• [Presentation] Assessment of genetic and epigenetic modifications in hypoplatic left heart syndrome by disease-specific iPS cells (2014)
  • Author(s): Junko Kobayashi, Masashi Yoshida, Suguru Tarui, Yusuke Nagai, Shingo Kasahara, Keiji Naruse , Hiroshi Ito, Shunji Sano , Hidemasa Oh
  • Organizer: 第78回 日本循環器学会総会学術集会
  • Place of Presentation: 東京
• [Presentation] Intracoronary Cardiac Progenitor Cell Transfer to Treat Univentricular Heart Disease: A Phase 2 Randomized Controlled Clinical Trial (PERSEUS) (2014)
  • Author(s): Suguru Tarui, Shinichi Ohtsuki, Daiki Ousaka, Takahiro Eitoku, Maiko Kondo, Junko Kobayashi, Michihiro Okuyama, Shunta Ishigami, Kenji Baba, Sadahiko Arai, Takuya Kawabata, Ko Yoshizumi, Yosuke Kuroko, Tatsuo Iwasaki, Shuhei Sato, Shingo Kasahara, Shunji Sano, and Hidemasa Oh
  • Organizer: 第78回 日本循環器学会総会学術集会
  • Place of Presentation: 東京
• [Presentation] 心不全への幹細胞移植療法 (2013)
  • Author(s): 王 英正
  • Organizer: 岡山先端医学研究会
  • Place of Presentation: 岡山
  • Invited
• [Presentation] 希少難治性心不全への心臓内幹細胞を用いた再生医療 (2013)
  • Author(s): 王 英正
  • Organizer: 青森臨床循環器研究会
  • Place of Presentation: 青森
  • Invited
• [Presentation] 希少難治性心不全に対する心臓内幹細胞を用いた再生医療 (2013)
  • Author(s): 王 英正
  • Organizer: 岡山大学知恵の見本市2013
  • Place of Presentation: 岡山
  • Invited
• [Presentation] 先天性心疾患に対する自己心臓内幹細胞による再生医療 (2013)
  • Author(s): 王 英正
  • Organizer: 第116回日本小児科学会学術集会
  • Place of Presentation: 広島
  • Invited
• [Presentation] Intracoronary delivery of cardiac progenitor cells in patients with hypoplastic left heart syndrome. (2013)
  • Author(s): Oh H, Tarui S, Ohtsuki S, Sano S
  • Organizer: The 30th International Society for Heart Research
  • Place of Presentation: サンディエゴ
  • Invited
• [Presentation] 心不全への幹細胞移植療法 (2013)
  • Author(s): 王 英正
  • Organizer: 第3回先端医学研究会at OU
  • Place of Presentation: 岡山
  • Invited
• [Presentation] 子どもの難治性心不全に対する幹細胞移植療法の取り組み (2013)
  • Author(s): 王 英正
  • Organizer: 公開セミナーはあとネット兵庫
  • Place of Presentation: 神戸
  • Invited
• [Presentation] Factors-based human cardiomyocytes differentiation exhibits defective maturation and excitation through aberrant calcium handling proteins. (2013)
  • Author(s): Tarui S, Kobayashi J，Hirata M, Yoshida M, Tateishi A, Arai S, Kasahara S,Ito H, Sano S, Oh H.
  • Organizer: The 21st annual meeting of the Asian society for cardiovascular and thoracic surgery
  • Place of Presentation: 神戸
• [Presentation] Patient-specific induced pluripotent stem cells recapitulate the models of hypoplastic left heart syndrome. (2013)
  • Author(s): Kobayashi J, Yoshida M, Tarui S, Hirata M, Tateishi A, Arai S, Kasahara S, K Takahashi, K Naruse, Sano S, Oh H.
  • Organizer: The 21st annual meeting of the Asian society for cardiovascular and thoracic surgery
  • Place of Presentation: 神戸
• [Presentation] Cardiac progenitor cell therapy in patients with hypoplastic left heart syndrome. (2013)
  • Author(s): S Sano, H Oh, S Tarui, S Ohtsuki, S Kasahara.
  • Organizer: American Association for Thoracic Surgery.
  • Place of Presentation: ミネアポリス
• [Presentation] Lineage induction of patient-specific iPS cells identifies the cardiac transcriptional repression during myocardial growth and patterning in HLHS. (2013)
  • Author(s): Kobayashi J, Yoshida M, Tarui S, Hirata M, Tateishi A, Arai S, Kasahara S, K Takahashi, K Naruse, Sano S, Oh H.
  • Organizer: TAKAO Symposium
  • Place of Presentation: 東京
• [Presentation] Directed differentiation of patient-specific induced pluripotent stem cells identifies the cardiac transcriptional repression during myocardial growth and patterning in hypoplastic left heart syndrome. (2013)
  • Author(s): Kobayashi J, Yoshida M, Tarui S, Hirata M, Tateishi A, Arai S, Kasahara S, K Takahashi, K Naruse, Sano S, Oh H.
  • Organizer: American Heart Association
  • Place of Presentation: ダラス
• [Presentation] 疾患特異的iPS細胞の樹立と左心低形成症候群の心臓発生異常の解明 (2013)
  • Author(s): 小林純子，樽井 俊，平田昌敬，川畑拓也，黒子洋介，立石篤史，吉積 功，新井禎彦，笠原真悟，佐野俊二，王 英正
  • Organizer: 日本外科学会 Young Researcher Award
  • Place of Presentation: 福岡
• [Book] 循環器内科：先天性心疾患外科手術における再生医療 (2014)
  • Author(s): 樽井 俊、王 英正、佐野俊二、
  • Total Pages: 7
  • Publisher: 医学出版
• [Patent(Industrial Property Rights)] Pluripotent stem cell derived from cardiac tissue (2013)
  • Inventor(s): Hidemasa Oh
  • Industrial Property Rights Holder: Hidemasa Oh
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-09-09
  • Acquisition Date: 2014-09-08
  • Overseas
• [Patent(Industrial Property Rights)] Preparation for treating heart disease used in cell therapy. (2013)
  • Inventor(s): 王 英正
  • Industrial Property Rights Holder: 王 英正
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-04-01
  • Acquisition Date: 2013-04-09
  • Overseas
• [Patent(Industrial Property Rights)] 細胞移植療法に用いられる心疾患治療薬 (2013)
  • Inventor(s): 王 英正
  • Industrial Property Rights Holder: 王 英正
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-04-01
  • Acquisition Date: 2014-03-14