Development of self-growing vascular graft using decellularized vascular tissue and human iPS cell-derived vascular cells

• Project/Area Number: 17H04291
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Kyoto University
• Principal Investigator: Ikeda Tadashi 京都大学, 医学研究科, 准教授 (40281092)
• Co-Investigator(Kenkyū-buntansha): 湊谷 謙司 京都大学, 医学研究科, 教授 (20393241) ; 岸田 晶夫 東京医科歯科大学, 生体材料工学研究所, 教授 (60224929) ; 升本 英利 国立研究開発法人理化学研究所, 生命機能科学研究センター, 上級研究員 (70645754)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 血管再生 / iPS細胞 / 移植・再生医療 / 循環器・高血圧 / 再生医学 / バイオテクノロジー / 細胞・組織 / 再生医療 / 脱細胞グラフト / ヒトiPS細胞

Outline of Final Research Achievements

In the present study, we aimed to develop methods to prepare xenogeneic decellularized vascular grafts and to re-seed purified human iPS cell-derived vascular endothelial cells on the decellularized grafts to establish a self-growing vascular grafts for clinical use. Here we established a method to prepare highly purified human iPS cell-derived vascular endothelial cells and to recellularize the decellularized grafts. We also found that xenogeneic vascular grafts can be recellularized in the body of xenogeneic animal with fair recellularization.

Academic Significance and Societal Importance of the Research Achievements

今後増加が予想される虚血性心疾患および下肢虚血性疾患に対する外科的バイパス手術における小口径バイパスグラフトは医療材料として今後ますます重要性が増すものと思われる。本研究成果は動物由来の脱細胞組織に対してヒトiPS細胞由来の血管細胞を播種・再細胞化することによる、いわゆる「ヒト化」血管グラフトを量的制限なく供給しうるための基礎研究的基盤を与えるものであり、医療経済を含む社会的な意義が高いものと考えられる。

Research Products

• [Int'l Joint Research] ハノーファー医科大学(ドイツ)
• [Int'l Joint Research] ハノーファー医科大学(ドイツ)
• [Journal Article] Management of retrosternal adhesion after median sternotomy by controlling degradation speed of a dextran and ε-poly (L-lysine)-based biocompatible glue (2020)
  • Author(s): Takai F, Takeda T, Yamazaki K, Ikeda T, Hyon SH, Minatoya K, Masumoto H.
  • Journal Title: Gen Thorac Cardiovasc Surg Volume: - Issue: 8 Pages: 793-800
  • DOI: 10.1007/s11748-020-01297-3
  • Peer Reviewed
• [Journal Article] The N-terminal lectin-like domain of thrombomodulin reduces acute lung injury without anticoagulant effects in a rat cardiopulmonary bypass model. (2020)
  • Author(s): Itonaga T, Hirao S, Yamazaki K, Ikeda T, Minatoya K, Masumoto H.
  • Journal Title: Gen Thorac Cardiovasc Surg Volume: - Issue: 8 Pages: 785-792
  • DOI: 10.1007/s11748-020-01292-8
  • Peer Reviewed
• [Journal Article] Basic fibroblast growth factor attenuates left-ventricular remodeling following surgical ventricular restoration in a rat ischemic cardiomyopathy model. (2020)
  • Author(s): Nagasawa A, Masumoto H, Yanagi S, Kanemitsu N, Ikeda T, Tabata Y, Minatoya K.
  • Journal Title: Gen Thorac Cardiovasc Surg Volume: 68(4) Issue: 4 Pages: 311-318
  • DOI: 10.1007/s11748-019-01187-3
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of Engineering Plastics Plasticized Using Supercritical CO2 (2020)
  • Author(s): Watanabe M, Hashimoto Y, Kimura T, Kishida A.
  • Journal Title: Polymers (Basel) Volume: 12(1) Issue: 1 Pages: 134-134
  • DOI: 10.3390/polym12010134
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA-145-loaded poly(lactic-co-glycolic acid) nanoparticles attenuate venous intimal hyperplasia in a rabbit model. (2019)
  • Author(s): Nishio H, Masumoto H, Sakamoto K, Yamazaki K, Ikeda T, Minatoya K.
  • Journal Title: J Thorac Cardiovasc Surg Volume: In press Issue: 6 Pages: 2242-2251
  • DOI: 10.1016/j.jtcvs.2018.08.115
  • Peer Reviewed
• [Journal Article] On-pump beating CABG concomitant with bilateral living-donor lobar lung transplantation. (2019)
  • Author(s): Ueyama K, Miyahara S, Ide Y, Sakamoto K, Kanemitsu H, Yamazaki K, Ikeda T, Aoyama A, Date H, Minatoya K.
  • Journal Title: Heart Lung Volume: 48 Issue: 2 Pages: 166-168
  • DOI: 10.1016/j.hrtlng.2018.08.008
  • Peer Reviewed
• [Journal Article] Chronic optical pacing conditioning of h-iPSC engineered cardiac tissues. (2019)
  • Author(s): Dwenger M, Kowalski WJ, Ye F, Yuan F, Tinney JP, Setozaki S, Nakane T, Masumoto H, Campbell P, Guido W, Keller BB.
  • Journal Title: J Tissue Eng Volume: 10 Pages: 204173141984174-204173141984174
  • DOI: 10.1177/2041731419841748
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Extracellular Matrix Induces Periodontal Ligament Reconstruction In Vivo (2019)
  • Author(s): Nakamura Naoko、Ito Ai、Kimura Tsuyoshi、Kishida Akio
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 13 Pages: 3277-3277
  • DOI: 10.3390/ijms20133277
  • Peer Reviewed / Open Access
• [Journal Article] Re-epithelialization and remodeling of decellularized corneal matrix in a rabbit corneal epithelial wound model (2019)
  • Author(s): Hashimoto Yoshihide、Funamoto Seiichi、Sasaki Shuji、Negishi Jun、Hattori Shinya、Honda Takako、Kimura Tsuyoshi、Kobayashi Hisatoshi、Kishida Akio
  • Journal Title: Materials Science and Engineering: C Volume: 102 Pages: 238-246
  • DOI: 10.1016/j.msec.2019.04.024
  • Peer Reviewed
• [Journal Article] A hybrid small‐diameter tube fabricated from decellularized aortic intima‐media and electrospun fiber for artificial small‐diameter blood vessel (2019)
  • Author(s): Wu Pingli、Nakamura Naoko、Morita Hiroko、Nam Kwangwoo、Fujisato Toshiya、Kimura Tsuyoshi、Kishida Akio
  • Journal Title: Journal of Biomedical Materials Research Part A Volume: 107 Issue: 5 Pages: 1064-1070
  • DOI: 10.1002/jbm.a.36631
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A fibrin‐coated pericardial extracellular matrix prevented heart adhesion in a rat model (2018)
  • Author(s): Funamoto Seiichi、Hashimoto Yoshihide、Kishida Akio、Negishi Jun
  • Journal Title: Journal of Biomedical Materials Research Part B: Applied Biomaterials Volume: 107 Issue: 4 Pages: 1088-1094
  • DOI: 10.1002/jbm.b.34201
  • Peer Reviewed
• [Journal Article] Human iPS cell-derived cardiac tissue sheets for functional restoration of infarcted porcine hearts. (2018)
  • Author(s): Ishigami M, Masumoto H, Ikuno T, Aoki T, Kawatou M, Minakata K, Ikeda T, Sakata R, Yamashita JK, Minatoya K.
  • Journal Title: PLoS One. Volume: 13 Issue: 8 Pages: e0201650-e0201650
  • DOI: 10.1371/journal.pone.0201650
  • NAID: 120006552912
  • Peer Reviewed / Open Access
• [Journal Article] Sustained release of basic fibroblast growth factor using gelatin hydrogel improved left ventricular function through the alteration of collagen subtype in a rat chronic myocardial infarction model. (2018)
  • Author(s): Li Z, Masumoto H, Jo JI, Yamazaki K, Ikeda T, Tabata Y, Minatoya K.
  • Journal Title: Gen Thorac Cardiovasc Surg. Volume: 66 Issue: 11 Pages: 641-647
  • DOI: 10.1007/s11748-018-0969-z
  • Peer Reviewed
• [Journal Article] A therapeutic angiogenesis of sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel sheets in a canine chronic myocardial infarction model. (2018)
  • Author(s): Kumagai M, Minakata K, Masumoto H, Yamamoto M, Yonezawa A, Ikeda T, Uehara K, Yamazaki K, Ikeda T, Matsubara K, Yokode M, Shimizu A, Tabata Y, Sakata R, Minatoya K.
  • Journal Title: Heart Vessels Volume: 33 Issue: 10 Pages: 1251-1257
  • DOI: 10.1007/s00380-018-1185-6
  • Peer Reviewed
• [Journal Article] Therapeutic angiogenesis by local sustained release of microRNA-126 using poly lactic-co-glycolic acid nanoparticles in murine hindlimb ischemia. (2017)
  • Author(s): Tsumaru S, Masumoto H, Minakata K, Izuhara M, Yamazaki K, Ikeda T, Ono K, Sakata R, Minatoya K.
  • Journal Title: J Vasc Surg. Volume: 印刷中 Issue: 4 Pages: 1209-1215
  • DOI: 10.1016/j.jvs.2017.08.097
  • Peer Reviewed / Open Access
• [Journal Article] Efficient and robust differentiation of endothelial cells from human induced pluripotent stem cells via lineage control with VEGF and cyclic AMP. (2017)
  • Author(s): Ikuno T, Masumoto H, Yamamizu K, Yoshioka M, Minakata K, Ikeda T, Sakata R, Yamashita JK
  • Journal Title: PLoS One Volume: 12 Issue: 3 Pages: e0173271-e0173271
  • DOI: 10.1371/journal.pone.0173271
  • NAID: 120005997909
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Chronic downstream aortic lesions after surgical repair of acute aortic dissection (2019)
  • Author(s): 湊谷 謙司、山﨑 和裕、金光 ひでお、坂本 和久、川東 正英、境 次郎、工藤 雅文、井出 雄二郎、池田 義
  • Organizer: 第119回日本外科学会定期学術集会
• [Presentation] iPS細胞由来三次元人工心臓組織作製技術の心臓再生医療への応用の試み (2019)
  • Author(s): 升本 英利、川東 正英、金光 ひでお、山﨑 和裕、池田 義、湊谷 謙司
  • Organizer: 第119回日本外科学会定期学術集会
• [Presentation] 胸腹部大動脈瘤人工血管置換術の治療戦略 (2019)
  • Author(s): 湊谷 謙司、山﨑 和裕、金光 ひでお、坂本 和久、川東 正英、境 次郎、工藤 雅文、井出 雄二郎、池田 義
  • Organizer: 第47回日本血管外科学会学術総会
• [Presentation] 循環器の再生医療を支える組織工学 DDSからiPS細胞治療まで (2019)
  • Author(s): 升本 英利
  • Organizer: 第40回日本炎症・再生医学会
• [Presentation] ヒトiPS細胞由来心血管系細胞多層体移植による心臓再生治療に向けた前臨床有効性試験 (2019)
  • Author(s): 升本 英利
  • Organizer: 第72回日本胸部外科学会定期学術集会
• [Presentation] iPS細胞由来心血管系細胞を用いた心臓再生医療 (2019)
  • Author(s): 升本 英利
  • Organizer: 第33回日本冠疾患学会学術集会
  • Invited
• [Presentation] iPS細胞から作製した人工心臓組織を用いた再生医療・疾患再現・創薬研究の試み (2019)
  • Author(s): 升本 英利
  • Organizer: 理研BDR-兵庫県立こども病院 第4回ジョイントシンポジウム
• [Presentation] Preclinical Efficacy Studies of Human iPS Cell-derived Cardiac Tissue Transplantation onto Animal Heart Disease Models (2019)
  • Author(s): Masumoto H, Hirao S, Takimoto S, Kawatou M, Ikeda T, Tabata Y, Yamashita JK, Minatoya K
  • Organizer: AHA Scientific Sessions 2019
  • Int'l Joint Research
• [Presentation] Evaluations for patency and recellularization of decellularized vascular grafts with high hydrostatic pressure method in a xeno-implantation animal model (2019)
  • Author(s): Kurokawa S, Masumoto H, Hashimoto Y, Funamoto S, Ikeda T, Kishida A, Minatoya K
  • Organizer: AHA Scientific Sessions 2019
  • Int'l Joint Research
• [Presentation] The N-terminal lection-like domain of thrombomodulin reduces acute lung injury without anticoagulant effects in a rat cardiopulmonary bypass model (2019)
  • Author(s): Itonaga T, Masumoto H, Yamazaki K, Ikeda T, Minatoya K
  • Organizer: AHA Scientific Sessions 2019
  • Int'l Joint Research
• [Presentation] Drug Delivery System-based Cardiovascular Regenerative Medicine: From Bench to Bedside (2019)
  • Author(s): Masumoto H
  • Organizer: The 15th US-Japan Symposium on Drug Delivery Systems
  • Int'l Joint Research / Invited
• [Presentation] 心臓再生医療用のヒトiPS細胞由来心血管系細胞多層体の開発． (2018)
  • Author(s): 升本 英利，中根 武一郎，平尾 慎吾，瀧本 真也，李 子澎，金光 ひでお，植山 浩二，山﨑 和裕，池田 義，田畑 泰彦，山下 潤，湊谷 謙司
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] マウス下肢虚血モデルにおけるゼラチンスポンジを用いたiPS細胞由来血管構成細胞移植による血流改善および血管再生効果の検討 (2018)
  • Author(s): 津丸 真一，升本 英利，川東 正英，幾野 毅，金光 ひでお，植山 浩二，山﨑 和裕，池田 義，湊谷 謙司
  • Organizer: 第46回日本血管外科学会学術総会
• [Presentation] 下大静脈が心尖部と同側にある単心室に対するTCPC手術 (2018)
  • Author(s): 池田 義，井出 雄二郎，馬場 志郎，平田 拓也，赤木 健太郎，松田 浩一，湊谷 謙司
  • Organizer: 第54回日本小児循環器学会総会・学術集会
• [Presentation] 可及的に房室弁形態を温存する完全型房室中隔欠損修復手術 (2018)
  • Author(s): 池田 義，井出 雄二郎，坂本 和久，金光 ひでお，山﨑 和裕，湊谷 謙司
  • Organizer: 第71回日本胸部外科学会定期学術集会
• [Presentation] 曲面形状を有するePTFE肺動脈弁の作成とその弁機能の検討 (2018)
  • Author(s): 池田 義，井出 雄二郎，城 麻衣子，坂本 和久，金光 ひでお，山﨑 和裕，湊谷 謙司
  • Organizer: 第71回日本胸部外科学会定期学術集会
• [Presentation] ラット皮下移植実験による人工血管生体組織適合性についての検討． (2018)
  • Author(s): 藤原 靖恵，平尾 慎吾，川東 正英，升本 英利，金光 ひでお，山﨑 和裕，池田 義，湊谷 謙司．
  • Organizer: 第71回日本胸部外科学会定期学術集会
• [Presentation] Transduction of micro RNA-145 using poly lactic-co-glycolic acid nanoparticles attenuates venous intimal hyperplasia in a rabbit vein graft disease model (2018)
  • Author(s): Nishio H, Masumoto H, Yamazaki K, Ikeda T, Minatoya K.
  • Organizer: European Society of Cardiology (ESC) Congress 2018
  • Int'l Joint Research
• [Presentation] Human iPS Cell-Derived Cardiac Tissue Transplantation to a Rat Unloaded Ischemic Heart Model Mimicking Left Ventricular Assist Device Implantation. (2018)
  • Author(s): Heima D, Masumoto H, Kawatou M, Osada H, Ikeda T, Tabata Y, Minatoya K, Yamashita J.K.
  • Organizer: AHA (American Heart Association) Scientific Sessions 2018
  • Int'l Joint Research
• [Presentation] 新肺動脈吻合部の移動により冠動脈の圧排を回避できた動脈スイッチ手術の1例 (2017)
  • Author(s): 池田 義，中田 朋宏，井出 雄二郎，中津 太郎，坂本 和久，金光 ひでお，山﨑 和裕，植山 浩二，湊谷 謙司
  • Organizer: 第70回日本胸部外科学会定期学術集会
• [Presentation] 修正大血管転移症、心尖部―上下大静脈同側例に対して、心外導管型TCPCを施行した1例 (2017)
  • Author(s): 矢次 遥，池田 義，中田 明宏，山﨑 和裕，金光 ひでお，坂本 和久，中津 太郎，山下 剛生，湊谷 謙司，馬場 志郎，平田 拓也
  • Organizer: 第31回日本小児循環器学会近畿・中四国地方会
• [Book] 先端医療シリーズ50 「循環器疾患の最新医療」 (2019)
  • Author(s): 升本 英利
  • Total Pages: 512
  • Publisher: 寺田国際事務所/先端医療技術研究所
  • ISBN: 9784925089623
• [Remarks] 京都大学 心臓血管外科
  • URL: http://kyoto-cvs.jp/