Adipose tissue derived regenerative cells & cytokine modification factor

• Project/Area Number: 16K09425
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kanazawa University
• Principal Investigator: Takamura Masayuki 金沢大学, 医学系, 教授 (60362000)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 再生医療 / 重症心不全 / 脂肪由来幹細胞 / サイトカイン / 臨床心臓病学 / 再生医療開発 / 心不全 / 脂肪組織 / インスリン抵抗性 / 炎症

Outline of Final Research Achievements

My research project were focused and continued to establish the regenerative medicine in the field of cardiovascular diseases. In particular, development of myocardial regeneration therapy and for severe heart failure and vascularization therapy for severe peripheral limb ischemia had been conducted. In addition, the functional analysis of surplus cells in clinical regenerative trial, animal experiments have been conducted simultaneously to establish elite stem cells that are optimal for regenerative medicine and to elucidate their mechanisms.

Academic Significance and Societal Importance of the Research Achievements

循環器領域における再生医療の実用化は、高齢社会における健康長寿を目指す上で、極めて重要な領域であると期待されています。今回の脂肪組織由来再生細胞の心機能改善や血管機能改善の機序解明と有効性向上のための研究成果は、国際学会でも注目されました。
今後は、培養細胞での検討結果、動物実験での検討にヒト臨床試験結果を総合して考察し、重症心不全、血管不全患者に対する間葉系幹細胞を用いた、より安全で、より有効な再生医療実現を加速させる予定です。

Research Products

• [Journal Article] Coronary sinus catheter placement via left cubital vein for phrenic nerve stimulation during pulmonary vein isolation (2019)
  • Author(s): Chikata Akio、Kato Takeshi、Usuda Kazuo、Fujita Shuhei、Maruyama Michiro、Otowa Kan-ichi、Takashima Shin-ichiro、Murai Hisayoshi、Usui Soichiro、Furusho Hiroshi、Kaneko Shuichi、Takamura Masayuki
  • Journal Title: Heart and Vessels Volume: 2 Issue: 10 Pages: 1710-1716
  • DOI: 10.1007/s00380-019-01402-4
  • Peer Reviewed / Open Access
• [Journal Article] Adipose tissue‐derived stem cells prevent fibrosis in murine steatohepatitis by suppressing IL‐17‐mediated inflammation (2019)
  • Author(s): Yamato Masatoshi、Sakai Yoshio、Mochida Hatsune、Kawaguchi Kazunori、Takamura Masayuki、Usui Soichiro、Seki Akihiro、Mizukoshi Eishiro、Yamashita Taro、Yamashita Tatsuya、Ishida Kousuke、Nasti Alessandro、Tuyen Ho Thuy Bich、Komura Takuya、Yoshida Keiko、Wada Takashi、Honda Masao、Kaneko Shuichi
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: - Issue: 8 Pages: 1432-1440
  • DOI: 10.1111/jgh.14647
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sphigosine-1-phosphate receptor 1 promotes neointimal hyperplasia in a mouse model of carotid artery injury. (2019)
  • Author(s): Kitano T, Takashima S, Inoue O, Goten C, Nomura A, Yoshioka K, Okajima M, Kaneko S, Takuwa Y, Takamura M.
  • Journal Title: Biochem. Biphys. Res. Communi. Volume: 511 Issue: 1 Pages: 179-184
  • DOI: 10.1016/j.bbrc.2019.02.047
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics of synthesized right-sided chest electrocardiograms in patients with acute pulmonary embolism (2019)
  • Author(s): Kusayama Takashi、Furusho Hiroshi、Kinoshita Masaki、Kaneko Shuichi、Usuda Kazuo、Takamura Masayuki
  • Journal Title: Journal of Cardiology Volume: 73 Issue: 4 Pages: 313-317
  • DOI: 10.1016/j.jjcc.2018.12.010
  • Peer Reviewed / Open Access
• [Journal Article] Endogenous muscle atrophy F-box is involved in the development of cardiac rupture after myocardial infarction (2019)
  • Author(s): Usui Soichiro、Chikata Akio、Takatori Osamu、Takashima Shin-ichiro、Inoue Oto、Kato Takeshi、Murai Hisayoshi、Furusho Hiroshi、Nomura Ayano、Zablocki Daniela、Kaneko Shuichi、Sadoshima Junichi、Takamura Masayuki
  • Journal Title: Journal of Molecular and Cellular Cardiology Volume: 126 Pages: 1-12
  • DOI: 10.1016/j.yjmcc.2018.11.002
  • Peer Reviewed / Open Access
• [Journal Article] Significant Association Between Coronary Artery Low-Attenuation Plaque Volume and Apnea-Hypopnea Index, But Not Muscle Sympathetic Nerve Activity, in Patients With Obstructive Sleep Apnea Syndrome (2018)
  • Author(s): Hamaoka Takuto、Murai Hisayoshi、Kaneko Shuichi、Usui Soichiro、Inoue Oto、Sugimoto Hiroyuki、Mukai Yusuke、Okabe Yoshitaka、Tokuhisa Hideki、Takashima Shinichiro、Kato Takeshi、Furusho Hiroshi、Kashiwaya Soichiro、Sugiyama Yu、Nakatsumi Yasuto、Takata Shigeo、Takamura Masayuki
  • Journal Title: Circulation Journal Volume: 82 Issue: 11 Pages: 2852-2860
  • DOI: 10.1253/circj.CJ-18-0237
  • NAID: 40021697272
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2018-10-25
  • Peer Reviewed
• [Journal Article] Comparison of Human Selenoprotein P Determinants in Serum between Our Original Methods and Commercially Available Kits (2018)
  • Author(s): Saito Yoshiro、Misu Hirofumi、Takayama Hiroaki、Takashima Shin-ichiro、Usui Soichiro、Takamura Masayuki、Kaneko Shuichi、Takamura Toshinari、Noguchi Noriko
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 41 Issue: 5 Pages: 828-832
  • DOI: 10.1248/bpb.b18-00046
  • NAID: 130006730702
  • ISSN: 0918-6158, 1347-5215
  • Year and Date: 2018-05-01
  • Peer Reviewed / Open Access
• [Journal Article] Optimal lesion size index to prevent conduction gap during pulmonary vein isolation (2018)
  • Author(s): Kanamori Naomi、Kato Takeshi、Sakagami Satoru、Saeki Takahiro、Kato Chieko、Kawai Keiichi、Chikata Akio、Takashima Shin‐ichiro、Murai Hisayoshi、Usui Soichiro、Furusho Hiroshi、Kaneko Shuichi、Takamura Masayuki
  • Journal Title: Journal of Cardiovascular Electrophysiology Volume: 29 Issue: 12 Pages: 1616-1623
  • DOI: 10.1111/jce.13727
  • Peer Reviewed
• [Journal Article] Differential effects of lipophilic and hydrophilic statins on muscle sympathetic nerve activity in heart failure with preserved left ventricular ejection fraction (2018)
  • Author(s): Tokuhisa Hideki、Murai Hisayoshi、Okabe Yoshitaka、Hamaoka Takuto、Sugimoto Hiroyuki、Mukai Yusuke、Inoue Oto、Takashima Shin-ichiro、Kato Takeshi、Usui Soichiro、Furusho Hiroshi、Kaneko Shuichi、Takamura Masayuki
  • Journal Title: Autonomic Neuroscience Volume: 213 Pages: 8-14
  • DOI: 10.1016/j.autneu.2018.04.006
  • Peer Reviewed
• [Journal Article] Occult constrictive pericardial disease emerging 40?years after chest radiation therapy: a case report (2018)
  • Author(s): Goten Chiaki、Murai Hisayoshi、Takashima Shin-ichiro、Kato Takeshi、Usui Soichiro、Furusho Hiroshi、Saeki Takahiro、Sakagami Satoru、Takemura Hirofumi、Kaneko Shuichi、Takamura Masayuki
  • Journal Title: BMC Cardiovascular Disorders Volume: 18 Issue: 1
  • DOI: 10.1186/s12872-018-0848-7
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of the risk factors for ventricular arrhythmias secondary to QT prolongation induced by papaverine injection during coronary flow reserve studies using a 4?Fr angio-catheter (2018)
  • Author(s): Okabe Yoshitaka、Otowa Kanichi、Mitamura Yasuhito、Murai Hisayoshi、Usui Soichiro、Kaneko Shuichi、Takamura Masayuki
  • Journal Title: Heart and Vessels Volume: 33 Issue: 11 Pages: 1358-1364
  • DOI: 10.1007/s00380-018-1175-8
  • Peer Reviewed
• [Journal Article] Endogenous Selenoprotein P, a Liver-Derived Secretory Protein, Mediates Myocardial Ischemia/Reperfusion Injury in Mice. (2018)
  • Author(s): Chikata A, Kato T, Usuda K, Fujita S, Maruyama M, Nagata Y, Sakagami S, Kanamori N, Yaegashi T, Saeki T, Kusayama T, Usui S, Furusho H, Kaneko S, Takamura M.
  • Journal Title: Int J Mol Sci. Volume: 19 Issue: 3 Pages: 878-878
  • DOI: 10.3390/ijms19030878
  • Peer Reviewed / Open Access
• [Journal Article] The CD45+ fraction in murine adipose tissue derived stromal cells harbors immune-inhibitory inflammatory cells. (2017)
  • Author(s): Nasti A, Sakai Y, Seki A, Buffa GB, Komura T, Mochida H, Yamato M, Yoshida K, Ho TTB, Takamura M, Usui S, Wada T, Honda M, Kaneko S.
  • Journal Title: Eur J Immunol. Volume: 47 Issue: 12 Pages: 2163-2174
  • DOI: 10.1002/eji.201646835
  • NAID: 120006454989
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Long-Term Administration of Eicosapentaenoic Acid Improves Post-Myocardial Infarction Cardiac Remodeling in Mice by Regulating Macrophage Polarization. (2017)
  • Author(s): Takamura M, Kurokawa K, Ootsuji H, Inoue O, Okada H, Nomura A, Kaneko S, Usui S.
  • Journal Title: J Am Heart Assoc Volume: 21 Issue: 2
  • DOI: 10.1161/jaha.116.004560
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Significant association between renal 123I-metaiodobenzylguanidine scintigraphy and muscle sympathetic nerve activity in patients with hypertension (2017)
  • Author(s): Takamura M, Murai H, Okabe Y, Okuyama Y, Hamaoka T, Mukai Y, Tokuhisa H, Inoue O, Takashima S, Kato T, Matsuo S, Usui S, Furusho H, Kaneko S.
  • Journal Title: J Nucl Cardiol Volume: Jan 9 Issue: 2 Pages: 363-371
  • DOI: 10.1007/s12350-016-0760-4
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Augmented sphingosine 1 phosphate receptor-1 signaling in cardiac fibroblasts induces cardiac hypertrophy and fibrosis through angiotensin II and interleukin-6. (2017)
  • Author(s): Ohkura SI, Usui S, Takashima SI, Takuwa N, Yoshioka K, Okamoto Y, Inagaki Y, Sugimoto N, Kitano T, Takamura M, Wada T, Kaneko S, Takuwa Y.
  • Journal Title: PLoS One. Volume: 12 Issue: 8 Pages: e0182329-e0182329
  • DOI: 10.1371/journal.pone.0182329
  • Peer Reviewed / Open Access
• [Journal Article] Adipose-derived regenerative cells exert beneficial effects on systemic responses following myocardial ischemia/reperfusion. (2016)
  • Author(s): Takamura M, Usui S, Inoue O, Ootsuji H, Takashima SI, Nomura A, Kato T, Murai H, Furusho H, Sakai Y, Kaneko S.
  • Journal Title: Cardiol J Volume: 23 Issue: 6 Pages: 685-693
  • DOI: 10.5603/cj.a2016.0061
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Altered gene expression in T-cell receptor signalling in peripheral blood leucocytes in acute coronary syndrome predicts secondary coronary events. (2016)
  • Author(s): Takashima S, Usui S, Kurokawa K, Kitano T, Kato T, Murai H, Furusho H, Oda H, Maruyama M, Nagata Y, Usuda K, Kubota K, Takeshita Y, Sakai Y, Honda M, Kaneko S, Takamura M.
  • Journal Title: Open Heart. Volume: 3(1) Issue: 1 Pages: e000400-e000400
  • DOI: 10.1136/openhrt-2016-000400
  • NAID: 120005830627
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sodium 4-Phenylbutyrate Attenuates Myocardial Reperfusion Injury by Reducing the Unfolded Protein Response. (2016)
  • Author(s): Takatori O, Usui S, Okajima M, Kaneko S, Ootsuji H, Takashima SI, Kobayashi D, Murai H, Furusho H, Takamura M.
  • Journal Title: J Cardiovasc Pharmacol Ther. Volume: Dec1
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Human CD271-positive Adipose Derived Stem Cells are the Angiogenic Subset with Less-aged and Less-fibrotic gene expression profile (2018)
  • Author(s): O. Inoue, S. Usui, S. Takashima, C. Goten, T. Hamaoka, H. Ootsuji, A. Nomura , K. Iino, H. Murai, H. Furusho, H. Takemura, S. Kaneko, M. Takamura
  • Organizer: AHA Scientific Sessions 2018
  • Int'l Joint Research
• [Presentation] Human CD271-positive Adipose Derived Stem Cells are the Angiogenic Subset with Pericytic Gene Profile and Enhanced Engraftment Capacity in Cell Therapy (2018)
  • Author(s): Oto Inoue, Soichiro Usui, Chiaki Goten, Takuto Hamaoka, Hideki Tokuhisa, Ayano Nomura, Hiroshi Ootsuji, Shin-ichiro Takashima, Hisayoshi Murai, Hiroshi Furusho, Kenji Iino, Hirofumi Takemura, Shuichi Kaneko, Masayuki Takamura
  • Organizer: 第82会日本循環器学会総会
• [Presentation] Chronic Hyperinsulinemia and Adipose Tissue Inflammation Decrease the Yield of Therapeutic Stem Cells in Patients with Cardiovascular Disease. (2017)
  • Author(s): 井上己音、高島伸一郎、薄井荘一郎、高村雅之
  • Organizer: 日本循環器学会総会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2017-03-17
• [Presentation] 脂肪由来間葉系細胞投与は肝遺伝子発言を制御し心筋虚血再灌流障害を軽減する (2017)
  • Author(s): 薄井荘一郎、高島伸一郎、井上己音、高村雅之
  • Organizer: 日本再生医療学会総会
  • Place of Presentation: 宮城県仙台市
  • Year and Date: 2017-03-07
• [Presentation] Adipose Tissue Inflammation and the Quality of Adipose-Derived Stem Cells in Patients with Cardiovascular Diseases (2017)
  • Author(s): Takamura M
  • Organizer: World Congress of Regenerative Medicine & Stem Cell.
  • Int'l Joint Research
• [Presentation] Sysytemic insulin resistance and adipose tissue inflamation predict decreased therapeutic mesenchymal stem cells for autologous transplantation in patients with cardiovascular disease. (2016)
  • Author(s): Inoue O, Usui S, Takashima S, Takamura M
  • Organizer: European Society of Cardiology Congress
  • Place of Presentation: Rome, Italy
  • Year and Date: 2016-08-27
  • Int'l Joint Research