Development of new vascular regenerative therapy by replacement of bone marrow cells with pluripotent stem cell-derived vascular progenitor cells.

• Project/Area Number: 21790757
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: YAMAHARA Kenichi 独立行政法人国立循環器病研究センター, 再生医療部, 室長 (50450888)
• Co-Investigator(Renkei-kenkyūsha): ITOH Hiroshi 慶應義塾大学, 医学部・腎臓内分泌代謝内科, 教授 (40252457) ; HOMMA Koichiro 慶応義塾大学, 医学部・腎臓内分泌代謝内科, 助教
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ES細胞 / マイクロRNA(miRNA) / 血管内皮細胞 / 血管平滑筋細胞 / 血管前駆細胞 / iPS細胞 / EPC(内皮前駆細胞) / マイクロアレイ

Research Abstract

We examined the therapeutic potential of ES cell-derived vascular progenitor cells as the alternative of bone marrow-derived vascular progenitor cells. Although human ES cell-derived vascular smooth muscle cells (VSMCs) obtained by our original method were at a rather immature state of differentiation, induction of miR-145 resulted in fully differentiated VSMCs. We also found that human ES-derived VSMCs at early passage possessed high proliferation and migration property, which might be a suitable cell source for vascular regeneration.

Research Products

• [Journal Article] Sustained-release adrenomedullin ointment accelerates wound healing of pressure ulcers. (2011)
  • Author(s): Harada K, Yamahara K, Ohnishi S, Otani K, Kanoh H, Ishibashi-Ueda H, Minamino N, Kangawa K, Nagaya N, Ikeda T.
  • Journal Title: RegulPept. Volume: 168 Pages: 21-26
  • Peer Reviewed
• [Journal Article] Adrenomedullin reduces expression of adhesion molecules on lymphatic endothelial cells. (2011)
  • Author(s): Jin D, Otani K, Yamahara K, Ikeda T, Nagaya N, Kangawa K.
  • Journal Title: RegulPept. Volume: 166 Pages: 21-27
  • Peer Reviewed
• [Journal Article] Allogeneic administration of fetal membrane-derived mesenchymal stem cells attenuates acute myocarditis in rats. (2010)
  • Author(s): Ishikane S, Yamahara K, Sada M, Harada K, Kodama M, Ishibashi-Ueda H, Hayakawa K, Mishima K, Iwasaki K, Fujiwara M, Kangawa K, Ikeda T.
  • Journal Title: J Mol Cell Cardiol. 49(5) Pages: 753-61
  • Peer Reviewed
• [Journal Article] Sirt1 plays an important role in mediating greater functionality of human ES/iPS-derived vascular endothelial cells. (2010)
  • Author(s): Homma K, Sone M, Taura D, Yamahara K, Suzuki Y, Takahashi K, Sonoyama T, Inuzuka M, Fukunaga Y, Tamura N, Itoh H, Yamanaka S, Nakao K.
  • Journal Title: Atherosclerosis. 212(1) Pages: 42-7
  • NAID: 120002598375
  • Peer Reviewed
• [Journal Article] Sirt1 plays an important role in mediating greater functionality of human ES/iPS-derived vascular endothelial cells. (2010)
  • Author(s): Homma K, Sone M, Taura D, Yamahara K, Suzuki Y, Takahashi K, Sonoyama T, Inuzuka M, Fukunaga Y, Tamura N, Itoh H, Yamanaka S, Nakao K.
  • Journal Title: Atherosclerosis. Volume: 212 Pages: 42-47
  • NAID: 120002598375
  • Peer Reviewed
• [Journal Article] Allogenic fetal membrane-derived mesenchymal stem cells contribute to renal repair in experimental glomerulonephritis. (2010)
  • Author(s): Tsuda H, Yamahara K, Ishikane S, Otani K, Nakamura A, Sawai K, Ichimaru N, Sada M, Taguchi A, Hosoda H, Tsuji M, Kawachi H, Horio M, Isaka Y, Kangawa K, Takahara S, Ikeda T.
  • Journal Title: Am J Physiol Renal Physiol. Volume: 299 Pages: 1004-1013
  • Peer Reviewed
• [Journal Article] Allogeneic administration of fetal membrane-derived mesenchymal stem cells attenuates acute myocarditis in rats. (2010)
  • Author(s): Ishikane S, Yamahara K, Sada M, Harada K, Kodama M, Ishibashi-Ueda H, Hayakawa K, Mishima K, Iwasaki K, Fujiwara M, Kangawa K, Ikeda T.
  • Journal Title: J Mol Cell Cardiol. Volume: 49 Pages: 753-761
  • Peer Reviewed
• [Journal Article] Angiogenic properties of sustained release platelet-rich plasma: characterization in-vitro and in the ischemic hind limb of the mouse. (2009)
  • Author(s): Bir SC, Esaki J, Marui A, Yamahara K, Tsubota H, Ikeda T, Sakata R.
  • Journal Title: J Vasc Surg. 50(4)
  • Peer Reviewed
• [Journal Article] Impaired recovery of blood flow after hind-limb ischemia in mice lacking guanylyl cyclase-A, a receptor for atrial and brain natriuretic peptides. (2009)
  • Author(s): Tokudome T, Kishimoto I, Yamahara K, Osaki T, Minamino N, Horio T, Sawai K, Kawano Y, Miyazato M, Sata M, Kohno M, Nakao K, Kangawa K.
  • Journal Title: Arterioscler Thromb Vasc Biol. 29(10) Pages: 1516-21
  • Peer Reviewed
• [Journal Article] Potential use of endothelial progenitor cells for regeneration of the vasculature. (2009)
  • Author(s): Yamahara K, Itoh H.
  • Journal Title: Ther Adv Cardiovasc Dis 3(1) Pages: 17-27
  • Peer Reviewed
• [Journal Article] Pathological role of angiostatin in heart failure : an endogenous inhibitor of mesenchymal stem-cell activation. (2009)
  • Author(s): Yamahara K, Min KD, Tomoike H, Kangawa K, Kitamura S, Nagaya N.
  • Journal Title: Heart. 95(4) Pages: 283-9
  • Peer Reviewed
• [Journal Article] Potential use of endothelial progenitor cells for regeneration of the vasculature. (2009)
  • Author(s): Yamahara K, Itoh H
  • Journal Title: Ther Adv Cardiovasc Dis 58 Pages: 2880-2892
  • Peer Reviewed
• [Presentation] The Role of Microrna-145 in Human Embryonic Stem Cell Differentiation Into Smooth Muscle Cells (2010)
  • Author(s): Yamaguchi S, Yamahara K, Homma K, Takesue S, Itoh H.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: シカゴ、米国
  • Year and Date: 2010-11-16
• [Presentation] ヒトES細胞由来血管平滑筋細胞の分化誘導におけるmiR-145の役割 (2010)
  • Author(s): 山口慎太郎、山原研一、本間康一郎、武末園子、伊藤裕
  • Organizer: 日本高血圧学会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-16
• [Presentation] ES・iPS細胞を用いた血管細胞分化・老化研究 (2010)
  • Author(s): 山原研一
  • Organizer: 第5回慶應臨床血管フォーラム
  • Place of Presentation: 慶應義塾大学総合医科学研究センター
  • Year and Date: 2010-01-29
• [Presentation] Aging of human ES cell-derived vascular cells: analysis of early and late passage cells. (2010)
  • Author(s): Yamahara K, Nishi T, Homma K, Takesue S, Yamaguchi S, Sone M, Itoh H.
  • Organizer: XX World Congress of the International Society for Heart Research (ISHR)
• [Presentation] iPS細胞由来血管前駆細胞を用いた新規下肢動脈閉塞性疾患治療法の開発 (2009)
  • Author(s): 山原研一
  • Organizer: 第50回日本脈管学会
  • Place of Presentation: ハイアットリージェンシー東京
  • Year and Date: 2009-10-30
• [Presentation] iPS細胞由来血管前駆細胞を用いた新規下肢動脈閉塞性疾患治療法の開発 (2009)
  • Author(s): 山原研一
  • Organizer: 第50回日本脈管学会 共催シンポジウム
• [Book] 血管の再生 (2008)
  • Author(s): 山原研一、曽根正勝、伊藤裕
  • Publisher: 真興出版
• [Remarks] ホームページ等