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2007 Fiscal Year Final Research Report Summary

Therapeutic Angiogenesis with Autologous Mesenchymal Stem Cell in Patients with Peripheral Artery Diseases: Mesenchymal Stem Cell Storing System

Research Project

Project/Area Number 18590815
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionHiroshima University

Principal Investigator

HIGASHI Yukihito  Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor (40346490)

Co-Investigator(Kenkyū-buntansha) YOSHIZUMI Masao  Hiroshima University, Graduate School of Biomedical Sciences, Professor (20282626)
KATO Yukio  Hiroshima University, Graduate School of Biomedical Sciences, Professor (10112062)
Project Period (FY) 2006 – 2007
KeywordsAngiogenesis / Mesenchymal stem cell / Cell store / Endotbelial function / Peripheral arterial disease / Buerger's disease
Research Abstract

Mesenchymal stem cells (MSCs) can differentiate into osteoblasts, nerve cells, skeletal muscle cells, and vascular endothelial cells in vivo and in vitro. It has been reported that MSC implantation induces active angiogenesis in ischemic limbs. We evaluated the effect of MSC implantation on limb blood flow (LBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, in rabbits with limb ischemia in which cultured MSC were implanted or saline was injected as a control group. LBF was measured using an electromagnetic flowmeter. A total of 10^6MSCs were implanted into each ischemic limb. Histological sections of ischemic muscle showed that capillary index was greater in the MSC implantation group than in the control group. Laser Doppler blood perfusion index was significantly increased in the MSC implantation group compared with that in the control group. LBF response to ACh was greater in the MSC group than in the control group. After administration of N^G-nitro-L-arginine, LBF response to ACh was similar in the MSC implantation group and control group. Vasodilatory effects of SNP in the two groups were similar. MSC implantation induces angiogenesis and augments endothelium-dependent vasodilation in a rabbit ischemic model through an increase in nitric oxide production.
It is clear that BM-MNC implantation is useful for patients with severe limb ischemia. However, patients were subjected by general anesthesia during BM-MNC aspiration. In the present study, we established the autologous MSC culture method. We are making a plan to store cultured MSC and to perform the autologous MSC implantation in patients with limb ischemia.

  • Research Products

    (27 results)

All 2008 2007 2006

All Journal Article (27 results) (of which Peer Reviewed: 11 results)

  • [Journal Article] Periodontal infection is associated with endothelial dysfunction in humans.2008

    • Author(s)
      Higashi Y, Jitsuiki D, Goto C, Umemura T, Nishioka K, Hidaka T, Takemoto T, Nakamura S, Nakagawa K, Oshima T, Chayama K, Yoshizumi M, Taguchi A.
    • Journal Title

      Hypertension. 51

      Pages: 446-453

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Periodontal infection is associated with endothelial dysfunction in humans2008

    • Author(s)
      Higashi, Y
    • Journal Title

      Hypertension 51

      Pages: 446-453

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Carvedilol improves endothelium-dependent vasodilation in patients with dilated cardiomyopathy.2007

    • Author(s)
      Nishioka K, Nakagawa K, Umemura T, Jitsuiki D, Ueda K, Goto C, Chayama K, Yoshizumi M, Higashi Y.
    • Journal Title

      Heart. 93

      Pages: 247-248

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Roles of ROCK and oxidative stress in the pathogenesis of aortic stiffness.2007

    • Author(s)
      Noma K, Goto C, Nishioka K, Jitsuiki D, Umemura T, Ueda K, Kimura M, Nakagawa K, Oshima T, Chayama K, Yoshizumi M, Liao JK, Higashi Y.
    • Journal Title

      J Am Coll Cardiol. 49

      Pages: 698-705

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Interaction of obesity and skeletal bone mineral density on tooth retention in Japanese postmenopausal women.2007

    • Author(s)
      Taguchi A, Tsuda M, Ohtsuka M, Nakamoto T, Inagaki K, Noguchi T, Kudo Y, Yoshizumi M, Higashi Y, Suei Y, Tanimoto K.
    • Journal Title

      Menopause. 14

      Pages: 500-504

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Sarpogrelate hydrochloride, a selective 5-HT_<2A> antagonist, improves vascular function in patients with peripheral arterial disease.2007

    • Author(s)
      Miyazaki M, Higashi Y, Goto C, Chayama K, Yoshizumi M, Sanada H, Sueda T.
    • Journal Title

      J Cardiovasc Pharm. 49

      Pages: 221-227

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Measurement of flow-mediated vasodilation of the brachial artery: a comparison of measurements in the sitting and supine positions.2007

    • Author(s)
      Soga J, Nishioka K, Nakamura S, Umemura T, Jitsuiki D, Hidaka T, Teragawa H, Goto C, Chayama K, Yoshizumi M, Higashi Y.
    • Journal Title

      Circ J. 71

      Pages: 736-740

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Repetition of ischemic preconditioning augments endothelium-dependent vasodilation in humans: role of endothelium-derived nitric oxide and endothelial progenitor cells.2007

    • Author(s)
      Kimura M, Goto C, Umemura T, Ueda K, Nishioka K, Jitsuiki D, Yoshizumi M, Chayama K, Higashi Y.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 27

      Pages: 1403-1410

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] The effects of different intensities of acute exercise on systemic hemodynamics and forearm vascular function in humans.2007

    • Author(s)
      Goto C, Nishioka K, Umemura T, Jitsuiki D, Sakaguchi A, Kawamura M, Yoshizumi M, Chayama K, Higashi Y:
    • Journal Title

      Am J Hypertens. 20

      Pages: 825-830

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans.2007

    • Author(s)
      Nishioka K, Hidaka T, Takemoto H, Nakamura S, Umemura T, Jitsuiki D, Soga J, Goto C, Chayama K, Yoshizumi M, Higashi Y.
    • Journal Title

      Hypertens Res. 30

      Pages: 775-780

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] The common and in vivo location-dependent markers for bone marrow mesenchymal stem cells isolated from jaw, iliac, femur, and tibia.2007

    • Author(s)
      Igarashi A, Segoshi K, Sakai Y, Pan H, Kanawa M, Higashi Y, Sugiyama M, Nakamura K, Kurihara H, Yamaguchi S, Tsuji K, Kawamoto T, Kato Y.
    • Journal Title

      Tissue Engineering. 13

      Pages: 2405-2417

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Corkscrew collaterals in thromboangitis obliterans (Buerger's disease).2007

    • Author(s)
      Fujii Y, Nishioka K, Yoshizumi M, Chayama K, Higashi Y.
    • Journal Title

      Circulation. 116

      Pages: 539-540

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Carvedilol improves endothelium-dependent vasodilation in patients with dilated cardiomyopathy2007

    • Author(s)
      Nishioka, K
    • Journal Title

      Heart 93

      Pages: 247-248

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Roles of ROCK and oxidative stress in the pathogenesis of aortic stiffness2007

    • Author(s)
      Noma, K
    • Journal Title

      J Am Coll Cardiol 49

      Pages: 698-705

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Interaction of obesity and skeletal bone mineral density on tooth retention in Japanese postmenopausal women2007

    • Author(s)
      Taguchi, A
    • Journal Title

      Menopause 14

      Pages: 500-504

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Sarpogrelate hydrochloride, a selective 5-HT_<2A> antagonist, improves vascular function in patients with peripheral arterial disease2007

    • Author(s)
      Miyazaki, M
    • Journal Title

      J Cardiovasc Pharm 49

      Pages: 221-227

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Measurement of flow-mediated vasodilation of the brachial artery : a comparison of measurements in the sitting and supine positions2007

    • Author(s)
      Soga, J
    • Journal Title

      Circ J 71

      Pages: 736-740

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Repetition of ischemic preconditioning augments endothelium-dependent vasodilation in humans : role of endothelium-derived nitric oxide and endothelial progenitor cells2007

    • Author(s)
      Kimura, M
    • Journal Title

      Arterioscler Thromb Vasc Biol 27

      Pages: 1403-1410

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The effects of different intensities of acute exercise on systemic hemodynamics and forearm vascular function in humans2007

    • Author(s)
      Goto, C
    • Journal Title

      Am J Hypertens 20

      Pages: 825-830

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans2007

    • Author(s)
      Nishioka, K
    • Journal Title

      Hyperteris Res 30

      Pages: 775-780

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The common and in vivo location-dependent markers for bone marrow mesenchymal stem cells isolated from jaw, iliac, femur, and tibia2007

    • Author(s)
      Igarashi, A
    • Journal Title

      Tissue Engineering 13

      Pages: 2405-2417

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Corkscrew collaterals in thromboangitis obliterans (Buerger's disease)2007

    • Author(s)
      Fujii, Y
    • Journal Title

      Circulation 116

      Pages: e539-e540

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Edaravone (3-methyl-l-phenyl-2-pyrazolin-5-one), a novel free radical scavenger, for cardiovascular diseases (review)2006

    • Author(s)
      Higashi, Y
    • Journal Title

      Recent Patent Reviews on Cardiovascular Drug 1

      Pages: 85-93

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Oxidative stress, endothelial function, and angiogenesis induced by cell therapy and gene therapy (review)2006

    • Author(s)
      Higashi, Y
    • Journal Title

      Curr Pharm Biotechnol 7

      Pages: 109-116

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Tetrahydrobiopterin improves aging-related impairment of endothelium-dependent vasodilation through increase in nitric oxide production and decrease in reactive oxygen species2006

    • Author(s)
      Higashi, Y
    • Journal Title

      Atherosclerosis 186

      Pages: 390-395

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Autologus bone-marrow mononuclear cell implantation induces angiogenesis and bone regeneration in a patient with compartment syndrome2006

    • Author(s)
      Umemura, T
    • Journal Title

      Circ J 70

      Pages: 1362-1364

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effects of acute administration of caffeine on vascular function2006

    • Author(s)
      Umemura, T
    • Journal Title

      Am J Cardiol 98

      Pages: 1538-1541

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-02-04  

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