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Autologous Bone-marrow Mononuclear Cell Implantation in Patients with Peripheral Artery Diseases : Mesenchymal Stem Cell Acute Culture Method and Assessment of Endothelial Function in Angiogenesis

Research Project

Project/Area Number 15590751
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, Assistant Professor, 大学院・医歯薬学総合研究科, 講師 (40346490)

Co-Investigator(Kenkyū-buntansha) YOSHIZUMI Masao  Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (20282626)
KATO Yukio  Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (10112062)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsAutologous bone-marrow mononuclear cell implantation / Endothelial function / Angiogenesis / Mesenchymal stem cell / Arteriosclerotic obliterance / Burger disease / Endothelial progenitor cell / Auto cell culture machine / 細胞自動培養増殖装置
Research Abstract

1.Limb ischemia is associated with endothelial dysfunction. To determine whether autologous bone-marrow mononuclear cell (BM-MNC) implantation improves endothelial function in patients with limb ischemia, we evaluated leg blood flow (LBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, using a mercury-filled silastic strain-gauge plethysmography before and after BM-MNC implantation in 7 patients with limb ischemia. After BM-MNC implantation, LBF response to ACh was enhanced. The vasodilatory effects of SNP before and after BM-MNC implantation were similar. These findings suggest that BM-MNC implantation augments endothelium-dependent vasodilation in patients with limb ischemia. (Circulation. 2004)
2.Although it is clear that BM-MNC implantation is useful for patients with severe limb ischemia, patients were subjected by general anesthesia during BM-MNC aspiration. In the present study, we established the autologous mesenchymal stem cell culture method. We are making a plan to perform the autologous mesenchymal stem cell implantation in patients with limb ischemia.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (60 results)

All 2005 2004 2003 Other

All Journal Article (46 results) Publications (14 results)

  • [Journal Article] Vascular function in patients with peripheral arterial disease : a comparison of upper and lower extremities.2005

    • Author(s)
      Sanada H
    • Journal Title

      Atherosclerosis 178

      Pages: 179-185

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nicorandil-induced vasodilation is, at least in part, due to endothelium-derived hyperpolarizing factor in humans.2005

    • Author(s)
      Ueda K
    • Journal Title

      J Cardiovasc Pharm 45

      Pages: 290-294

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angiotensin II type I receptor blocker and endothelial function in humans : role of nitric oxide and oxidative stress (review).2005

    • Author(s)
      Higashi Y
    • Journal Title

      Current Medicinal Chemistry-Cardiovascular & Hematological Agents

      Pages: 133-148

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of helicobacter pylori infection with systemic inflammation and endothelial dysfunction in healthy male subjects.2005

    • Author(s)
      Oshima T
    • Journal Title

      J Am Coll Cardiol

      Pages: 1219-1222

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular markers distinguish bone marrow mesenchymal stem cells from fibroblasts.2005

    • Author(s)
      Ishi M
    • Journal Title

      Biochem Biophys Res Commun

      Pages: 297-303

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Vascular function in patients with peripheral arterial disease : a comparison of upper and lower extremities.2005

    • Author(s)
      Sanada M
    • Journal Title

      Atherosclerosis 178

      Pages: 179-185

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angiotensin II type I receptor blocker and endothelial function in humans : role of nitric oxide and oxidative stress (review).2005

    • Author(s)
      Higashi Y
    • Journal Title

      CMC-Cardio & Hemato Agents 3

      Pages: 133-148

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of Helicobacter Pylori Infection with Systemic Inflammation and Endothelial Dysfunction in Healthy Male Subjects.2005

    • Author(s)
      Oshima T
    • Journal Title

      J Am Coll Cardiol 45

      Pages: 1219-1222

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular markers distinguish bone marrow mesenchymal stem cells from fibroblasts.2005

    • Author(s)
      Ishii M
    • Journal Title

      Biochem Biophys Res Commun 332

      Pages: 297-303

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Vascular function in patients with peripheral arterial disease : a comparison of upper and lower extremities.2005

    • Author(s)
      Sanada H, Higashi Y(他4名, 2番目)
    • Journal Title

      Atherosclerosis 178

      Pages: 179-185

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Nicorandil-induced vasodilation is, at least in part, due to endothelium-derived hyperpolarizing factor in humans.2005

    • Author(s)
      Ueda K, Higashi Y(他12名, 13番目)
    • Journal Title

      J Cardiovasc Pharm 45

      Pages: 290-294

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Angiotensin II type I receptor blocker and endothelial function in humans : role of nitric oxide and oxidative stress(review).2005

    • Author(s)
      Higashi Y(他2名)
    • Journal Title

      Current Medicinal Chemistry-Cardiovascular & Hematological Agents (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Association of helicobacter pylori infection with systemic inflammation and endothelial dysfunction in healthy male subjects.2005

    • Author(s)
      Oshima T, Higashi Y(他8名, 6番目)
    • Journal Title

      J Am Coll Cardiol (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Tetrahydrobiopterin improves aging-related impairment of endothelium-dependent vasodilation through increase in nitric oxide production and decrease in reactive oxygen species.2005

    • Author(s)
      Higashi Y(他10名)
    • Journal Title

      Atherosclerosis (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia.2004

    • Author(s)
      Higashi Y
    • Journal Title

      Circulation 109

      Pages: 1215-1218

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Exercise and endothelial function : role of endothelium-derived nitric oxide and oxidative stress in healthy subjects and hypertensive patients (review).2004

    • Author(s)
      Higashi Y
    • Journal Title

      Pharmacology and Therapeutics 102

      Pages: 87-96

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tooth loss is associated with an increased risk of hypertension in postmenopausal women.2004

    • Author(s)
      Taguchi A
    • Journal Title

      Hypertension 43

      Pages: 1297-1300

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Relation between C reactive protein concentrations and coronary microvascular endothelial function.2004

    • Author(s)
      Teragawa H
    • Journal Title

      Heart 90

      Pages: 750-754

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Forearm endothelial function and bone mineral loss in postmenopausal women.2004

    • Author(s)
      Sanada M
    • Journal Title

      Atherosclerosis 176

      Pages: 387-392

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of Edaravone, A novel free radical scavenger, on endothelium-dependent vasodilation in smokers.2004

    • Author(s)
      Jitsuiki D
    • Journal Title

      Am J Cardiol 94

      Pages: 1070-1073

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Apolipoprotein E phenotype affects the malondialdehyde-modified LDL concentration and forearm endothelial function in postmenopausal women.2004

    • Author(s)
      Tsuda M
    • Journal Title

      Clin Endoclinol 61

      Pages: 619-625

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Relation between C reactive protein concentrations and coronary microvascular endothelial function.2004

    • Author(s)
      Teragawa H
    • Journal Title

      Heart.2004 90

      Pages: 750-754

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Taguchi Forearm endothelial function and bone mineral loss in postmenopausal women.2004

    • Author(s)
      Sanada M
    • Journal Title

      Atherosclerosis 176

      Pages: 387-392

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of Edaravone, a novel free radical scavenger, on endothelium-dependent vasodilation in smokers.2004

    • Author(s)
      Jitsuiki D
    • Journal Title

      Am J Cardiol 94

      Pages: 1070-1073

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia.2004

    • Author(s)
      Higashi Y(他12名)
    • Journal Title

      Circulation 109

      Pages: 1215-1218

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Exercise and endothelial function : role of endothelium-derived nitric oxide and oxidative stress in healthy subjects and hypertensive patients (review).2004

    • Author(s)
      Higashi Y, Yoshizumi M.
    • Journal Title

      Pharmacology and Therapeutics 102

      Pages: 87-96

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Tooth loss is associated with an increased risk of hypertension in postmenopausal women.2004

    • Author(s)
      Taguchi A, Higashi Y(他9名, 10番目)
    • Journal Title

      Hypertension 43

      Pages: 1297-1300

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Relation between C reactive protein concentrations and coronary microvascular endothelial function.2004

    • Author(s)
      Teragawa H, Higashi Y(他7名, 5番目)
    • Journal Title

      Heart 90

      Pages: 750-754

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Forearm endothelial function and bone mineral loss in postmenopausal women.2004

    • Author(s)
      Sanada M, Higashi Y(他6名, 3番目)
    • Journal Title

      Atherosclerosis 176

      Pages: 387-392

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effect of Edaravone, A novel free radical scavenger, on endothelium-dependent vasodilation in smokers.2004

    • Author(s)
      Jitsuiki D, Higashi Y(他9名, 2番目)
    • Journal Title

      Am J Cardiol 94

      Pages: 1070-1073

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Apolipoprotein E phenotype affects the malondialdehyde-modified LDL concentration and forearm endothelial function in postmenopausal women.2004

    • Author(s)
      Tsuda M, Higashi Y(他7名, 3番目)
    • Journal Title

      Clin Endoclinol 61

      Pages: 619-625

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Low body mass index is a risk factor for impaired endothelium-dependent vasodilation in humans : role of nitric oxide and oxidative stress.2003

    • Author(s)
      Higashi Y
    • Journal Title

      J Am Coll Cardiol 42

      Pages: 256-263

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A comparison of low-dose and standard-dose oral estrogen on forearm endothelial function in early postmenopausal women.2003

    • Author(s)
      Sanada M
    • Journal Title

      J Clin Endocr Metab 88

      Pages: 1303-1309

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Comparison of forearm endothelial function between premenopausal and postmenopausal women with or without hypercholesterolemia.2003

    • Author(s)
      Sanada M
    • Journal Title

      Maturitas 44

      Pages: 307-315

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Smoking activates Rho-kinase in smooth muscle cells of forearm vasculature in humans.2003

    • Author(s)
      Noma K
    • Journal Title

      Hypertension 41

      Pages: 1102-1105

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] PDE5 inhibitor sildenafil citrate augments endothelium-dependent vasodilation in smokers.2003

    • Author(s)
      Kimura M
    • Journal Title

      Hypertension 41

      Pages: 1106-1110

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The effect of different intensities of exercise on endothelium-debendent vasodilation in humans : role of endothelium-dependent nitric oxide and oxidative stress.2003

    • Author(s)
      Goto C
    • Journal Title

      Circulation 108

      Pages: 530-535

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Myocardial bridging increases the risk of coronary spasm.2003

    • Author(s)
      Teragawa H
    • Journal Title

      Clin Cardiol 26

      Pages: 838-843

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Leptin causes nitric-oxide independent coronary artery vasodilation in humans.2003

    • Author(s)
      Matsuda K
    • Journal Title

      Hypertens Res 26

      Pages: 147-152

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of amlodipine and cilazapril treatment on platelet Ca2+ handling in spontaneously hypertensive rats.2003

    • Author(s)
      Oshima T
    • Journal Title

      Hypertens Res 26

      Pages: 901-906

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Azelnidipine : a viewpoint by Yukihito Higashi (guest commentaries).2003

    • Author(s)
      Higashi Y
    • Journal Title

      Drugs 63

      Pages: 2623-2624

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Response of the left anterior descending coronary artery to acetylcholine in patients with chest pain and angiographically normal coronary arteries.2003

    • Author(s)
      Matsuda K
    • Journal Title

      Am J Cardiol 92

      Pages: 1394-1398

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Method for assessing endothelial function in humans using a strain-gauge plethysmography : nitric oxide-dependent and -independent vasodilation(review).2003

    • Author(s)
      Higashi Y
    • Journal Title

      J Pharma Sci 93

      Pages: 399-404

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The effect of different intensities of exercise on endothelium-dependent vasodilation in humans : role of endothelium-dependent nitric oxide and oxidative stress.2003

    • Author(s)
      Goto C
    • Journal Title

      Circulation 108

      Pages: 530-535

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of amlodipine and cilazapril treatment on platelet Ca^<2+> handling in spontaneously hypertensive rats.2003

    • Author(s)
      Oshima T
    • Journal Title

      Hypertens Res 26

      Pages: 901-906

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Method for assessing endothelial function in humans using a strain-gauge plethysmography : nitric oxide-dependent and -independent vasodilation.2003

    • Author(s)
      Higashi Y
    • Journal Title

      J Pharma Sci 93

      Pages: 399-404

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Higashi Y(他11名): "Low body mass index is a risk factor for impaired endothelium-dependent vasodilation in humans : role of nitric oxide and oxidative stress"J Am Coll Cardiol. 42. 256-263 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sanada M, Higashi Y(他6名, 2番目): "A comparison of low-dose and standard-dose oral estrogen on forearm endothelial function in early postmenopausal women"J Clin Endocr Metab. 88. 1303-1309 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sanada M, Higashi Y(他6名, 2番目): "Comparison of forearm endothelial function between premenopausal and postmenopausal women with or without hypercholesterolemia"Maturitas. 44. 307-315 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Noma K, Higashi Y(他9名, 2番目): "Smoking activates Rho-kinase in smooth muscle cells of forearm vasculature in humans"Hypertension. 41. 1102-1105 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kimura M, Higashi Y(他9名, 2番目): "PDE5 inhibitor sildenafil citrate augments endothelium-dependent vasodilation in smokers"Hypertension. 41. 1106-1110 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Goto C, Higashi Y(他8名, 2番目): "The effect of different intensities of exercise on endothelium -dependent vasodilation in humans : role of endothelium-dependent nitric oxide and oxidative stress"Circulation. 108. 530-535 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Teragawa H.Higashi Y(他5名, 5番目): "Myocardial bridging increases the risk of coronary spasm"Clin Cardiol. 26. 838-843 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuda K, Higashi Y(他4名, 5番目): "Leptin causes nitric-oxide independent coronary artery vasodilation in humans"Hypertens Res. 26. 147-152 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Oshima T, Higashi Y(他8名, 4番目): "Effect of amlodipine and cilazapril treatment on platelet Ca2+ handling in spontaneously hypertensive rats"Hypertens Res. 26. 901-906 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hieashi Y.: "Azelnidipine : a viewpoint by Yukihito Higashi (guest commentaries)"Drugs. 63. 2623-2624 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuda K, HigashiY(他9名, 5番目): "Response of the left anterior descending coronary artery to acetylcholine in patients with chest pain and angiographically normal coronary arteries"Am J Cardiol. 92. 1394-1398 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Higashi Y, Yoshizumi M.: "Method for assessing endothelial function in humans using a strain-gauge plethysmography : nitric oxide-dependent and -independent vasodilation (review)"J Pharma Sci. 93. 399-404 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Higashi Y(他12名): "Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia"Circulation. 109. 1215-1218 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Higashi Y, Yoshizumi M.: "Exercise and endothelial function : role of endothelium-derived nitric oxide and oxidative stress in healthy subjects and hypertensive patients (review)"Pharmacology and Therapeutics. (In press). (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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