MHC-matched allogeneic transplantation of iPS cell-derived cardiomyocytes

• Project/Area Number: 26293182
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Shinshu University
• Principal Investigator: SHIBA Yuji 信州大学, 医学部附属病院, 准教授(特定雇用) (70613503)
• Co-Investigator(Kenkyū-buntansha): 瀬戸 達一郎 信州大学, 学術研究院医学系(医学部附属病院), 講師 (70362118)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 循環器内科学 / 再生医学 / 循環器 / 再生医療

Outline of Final Research Achievements

iPS cells were generated from fibroblasts from an animal with a homozygous MHC haplotype (HT4), and the cells were differentiated into cardiomyocytes (iPSC-CMs). Five HT4 heterozygous monkeys were subjected to myocardial infarction followed by direct intramyocardial injection of the iPSC-CMs. The grafted cardiomyocytes survived for 12 weeks with no evidence of immune rejection, and they showed indisputable electrical integration with host cardiomyocytes. In addition, transplantation of the iPSC-CMs improved cardiac contractile function; however, the incidence of VT was transiently but significantly increased when compared to the vehicle-treated control. MHC-matched allogeneic transplantation of iPSC-CMs regenerates infarcted non-human primate heart. Further research to control post-transplant arrhythmias is warranted.

Research Products

• [Journal Article] Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate heart (2016)
  • Author(s): Shiba Y, et al.
  • Journal Title: Nature Volume: 538 Pages: 388-391
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A young patient with atypical type-B Wolff-Parkinson-White syndrome accompanied by left ventricular dysfunction (2015)
  • Author(s): Takeuchi T, Tomita T, Kasai H, Kashiwagi D, Yoshie K, Yaguchi T, Oguchi Y, Kozuka A, Gautam M, Motoki H, Okada A, Shiba Y, AizawaK, Izawa A, Miyashita Y, Koyama J, Hongo M, Ikeda U
  • Journal Title: Journal of Arrhythmia Volume: 31巻 Issue: 1 Pages: 50-54
  • DOI: 10.1016/j.joa.2014.03.011
  • Peer Reviewed / Open Access
• [Journal Article] Transplantation of adipose tissue-derived stem cells improves cardiac contractile function and electrical stability in a rat myocardial infarction model. (2015)
  • Author(s): Gautam M., Fujita D., Kimura K., Ichikawa H., Izawa A., Hirose M., Kashihara T., Yamada M., Takahashi M., Ikeda U., Shiba Y.
  • Journal Title: Journal of molecular and cellular cardiology Volume: 81 Pages: 139-149
  • DOI: 10.1016/j.yjmcc.2015.02.012
  • Peer Reviewed / Open Access
• [Journal Article] Association between estimated glomerular filtration rate and peripheral arterial disease. (2015)
  • Author(s): Yamasaki S, Izawa A, Koshikawa M, Saigusa T, Ebisawa S, Miura T, Shiba Y, Tomita T, Miyashita Y, Koyama J, Ikeda U.
  • Journal Title: Journal of Cardiology Volume: 66 Issue: 5 Pages: 430-434
  • DOI: 10.1016/j.jjcc.2015.01.011
  • Peer Reviewed / Open Access
• [Journal Article] Differential roles of MMP-9 in early and late stages of dystrophic muscles in a mouse model of Duchenne muscular dystrophy (2015)
  • Author(s): Naoko Shiba, Daigo Miyazaki, Takahiro Yoshizawa, Kazuhiro Fukushima, Yuji Shiba, Yuji Inaba, Michihiro Imamura, Shin'ichi Takeda, Kenichi Koike, Akinori Nakamura
  • Journal Title: Biochimica et Biophysica Acta Volume: 1852 Issue: 10 Pages: 2170-2182
  • DOI: 10.1016/j.bbadis.2015.07.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] New Strategy for the Treatment of Myocarditis by Cell-Sheet Technology (2014)
  • Author(s): Shiba Y.
  • Journal Title: Circulation Journal Volume: 79 Issue: 1 Pages: 51-52
  • DOI: 10.1253/circj.CJ-14-1270
  • NAID: 130004704040
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] Electrical Integration of Human Embryonic Stem Cell-Derived Cardiomyocytes in a Guinea Pig Chronic Infarct Model. (2014)
  • Author(s): Shiba Y, Filice D, Fernandes S, Minami E, Dupras SK, Biber BV, Trinh P, Hirota Y, Gold JD.
  • Journal Title: J Cardiovasc Pharmacol Ther Volume: 19(4) Pages: 368-381
  • Peer Reviewed
• [Journal Article] 幹細胞由来心筋細胞移植による不整脈抑制作用 (2014)
  • Author(s): 柴 祐司
  • Journal Title: 週刊医学のあゆみ Volume: 248(2) Pages: 161-162
• [Presentation] シンポジウム2 脂肪組織由来幹細胞を用いた新たな血管再生治療． (2015)
  • Author(s): 柴 祐司
  • Organizer: 第56回日本脈管学会総会
  • Place of Presentation: 虎ノ門ヒルズ、東京都港区
  • Year and Date: 2015-10-29
• [Presentation] Preclinical transplantation study for pluripotent stem cell-derived cardiomyocytes in non-human primates. (2014)
  • Author(s): 柴 祐司
  • Organizer: 国際心臓研究学会(ISHR)日本部会
  • Place of Presentation: ウインクあいち（名古屋）
  • Year and Date: 2014-11-28 – 2014-11-29