Roles of bone marrow-derived cells in pathogenesis of pulmonary arterial hypertension associated with connective tissue diseases

• Project/Area Number: 21390300
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Keio University
• Principal Investigator: KUWANA Masataka 慶應義塾大学, 医学部, 准教授 (50245479)
• Co-Investigator(Kenkyū-buntansha): SETA Noriyuki 慶應義塾大学, 医学部, 助教 (40338372) ; SATOH Takashi 北里大学, 医療衛生学部, 助教 (90407114) ; FURUYA Yoshiaki 慶應義塾大学, 医学部, 助教 (30424154)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2011: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 膠原病学 / 肺動脈性肺高血圧症 / 強皮症 / 血管内皮前駆細胞 / 単球 / 血管新生 / 線維化 / 膠原病 / 血管リモデリング

Research Abstract

Pulmonary arterial hypertension(PAH) associated with systemic sclerosis(SSc) is one of intractable conditions with poor prognosis, but its pathogenic process is largely unknown. We have examined potential roles of endothelial progenitor cells(EPCs), which are involved in vascular repair, in the pathogenesis of PAH associated with SSc. As a result, EPCs in patients with SSc exhibited impaired vascular repair machinery, but had enhanced pro-fibrotic capacity. These EPC properties are the most prominent in SSc patients with PAH, and invasion capacity is augmented in EPCs derived from such patients. In summary, aberrant circulating EPC is a novel therapeutic target in PAH associated with SSc.

Research Products

• [Journal Article] Quantification of circulating endothelial progenitor cells in systemic sclerosis : a direct comparison of protocols (2012)
  • Author(s): Kuwana M, Okazaki Y
  • Journal Title: Ann Rheum Dis Volume: 71(4) Pages: 617-20
  • Peer Reviewed
• [Journal Article] Intracranial transplantation of monocyte-derived multipotential cells enhances recovery after ischemic stroke in rats (2012)
  • Author(s): Hattori H, Suzuki S, Okazaki Y, Suzuki N, Kuwana M
  • Journal Title: J Neurosci Res Volume: 90(2) Pages: 479-88
  • Peer Reviewed
• [Journal Article] Potential involvement of human circulating CD14^+ monocytes in tissuerepair and regeneration (2012)
  • Author(s): Seta N, Kuwana M
  • Journal Title: Inflammation and Regeneration Volume: 32 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Quantification of circulating endothelial progenitor cells in systemic sclerosis : a direct comparison of protocols (2012)
  • Author(s): Kuwana M, Okazaki Y
  • Journal Title: Annals of the Rheumatic Diseases Volume: 71 Issue: 4 Pages: 617-620
  • DOI: 10.1136/annrheumdis-2011-200713
  • Peer Reviewed
• [Journal Article] Association of Hepatocyte Growth Factor promoter polymorphism with severity of interstitial lung disease in Japanese patients with systemic sclerosis (2011)
  • Author(s): Hoshino K, Satoh T, Kawaguchi Y, Kuwana M
  • Journal Title: Arthritis Rheum Volume: 63(8) Pages: 2465-72
  • Peer Reviewed
• [Journal Article] Association of Hepatocyte Growth Factor promoter polymorphism with severity of interstitial lung disease in Japanese patients with systemic sclerosis (2011)
  • Author(s): Hoshino K, Satoh T, Kawaguchi Y, Kuwana M
  • Journal Title: Arthritis & Rheumatism Volume: 63 Issue: 8 Pages: 2465-2472
  • DOI: 10.1002/art.30415
  • Peer Reviewed
• [Journal Article] Effect of bosentan on systemic sclerosis-associated interstitial lung disease ineligible for cyclophosphamide therapy : a prospective open-label study (2011)
  • Author(s): Furuya Y, Kuwana M
  • Journal Title: The Journal of Rheumatology Volume: 38 Issue: 10 Pages: 2186-2192
  • DOI: 10.3899/jrheum.110499
  • Peer Reviewed
• [Journal Article] 膠原病-新たな治療戦略;膠原病診療の実際:全身性硬化症 (2010)
  • Author(s): 桑名正隆
  • Journal Title: 臨床と研究 Volume: 87(9) Pages: 1209-13
• [Journal Article] Enhanced angiogenic potency of monocytic endothelial progenitor cells in patients with systemic sclerosis (2010)
  • Author(s): Yamaguchi Y, Okazaki Y, Seta N, Satoh T, Takahashi K, Ikezawa Z, Kuwana M
  • Journal Title: Arthritis Res Ther Volume: 12(6)
  • Peer Reviewed
• [Journal Article] Mobilization of endothelial progenitor cells by intravenous cyclophosphamide in patients with systemic sclerosis : potential association with efficacy for interstitial lung disease (2010)
  • Author(s): Furuya Y, Okazaki Y, Kaji K, Sato S, Takehara K, Kuwana M
  • Journal Title: Rheumatology Volume: 49(12) Pages: 2375-80
  • Peer Reviewed
• [Journal Article] Interleukin-6 as a potential therapeutic target for pulmonary arterial hypertension (2010)
  • Author(s): Furuya Y, Satoh T, Kuwana M
  • Journal Title: Int J Rheumatol Volume: 2010 Pages: 720305-720305
  • Peer Reviewed
• [Journal Article] Derivation of multipotent progenitors from human circulating CD14+monocytes (2010)
  • Author(s): Seta N, Kuwana M
  • Journal Title: Exp Hematol Volume: 38(7) Pages: 557-63
  • Peer Reviewed
• [Journal Article] Enhanced angiogenic potency of monocytic endothelial progenitor cells in patients with systemic sclerosis (2010)
  • Author(s): Yamaguchi Y, Okazaki Y, Seta N, Satoh T, Takahashi K, Ikezawa Z, Kuwana M
  • Journal Title: Arthritis Research & Therapy Volume: 12
  • Peer Reviewed
• [Journal Article] 話題;強皮症の早期診断 (2010)
  • Author(s): 桑名正隆
  • Journal Title: リウマチ科 Volume: 44 Pages: 464-472
• [Journal Article] RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermato myositis : association with rapidly progressive interstitial lung disease (2009)
  • Author(s): Sato S, Hoshino K, Satoh T, Fujita T, Kawakami Y, Fujita T, Kuwana M
  • Journal Title: Arthritis & Rheumatism 60 Pages: 2193-2200
  • Peer Reviewed
• [Presentation] Angiogenesis and vasculogenesis in systemic sclerosis-review and gaps in the evidence (2012)
  • Author(s): Kuwana M
  • Organizer: 2nd Systemic Sclerosis World Congress(Madrid)
  • Year and Date: 2012-02-04
• [Presentation] Impaired in vivo neovascularization capacity of endothelial progenitor cells in patients with systemic sclerosis (2011)
  • Author(s): Kuwana M, Okazaki Y, Yasuoka H, Takeuchi T
  • Organizer: The 75th Annual Scientific Meeting of American College of Rheumatology
  • Place of Presentation: Chicago
  • Year and Date: 2011-11-07
• [Presentation] Impaired in vivo neovascularization capacity of endothelial progenitor cells in patients with systemic sclerosis (2011)
  • Author(s): Kuwana M, Okazaki Y, Yasuoka H, Takeuchi T
  • Organizer: The 75th Annual Scientific Meeting of American College of Rheumatology
  • Place of Presentation: McCormick Place West (Chicago)
  • Year and Date: 2011-11-07
• [Presentation] カレントシンポジウム;膠原病の診療最前線;強皮症 (2011)
  • Author(s): 桑名正隆
  • Organizer: 第55回日本リウマチ学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2011-07-20
• [Presentation] Organ involvement in early SSc (2011)
  • Author(s): Kuwana M
  • Organizer: 4th International Systemic Sclerosis Forum-Combating Morbidity and Mortality
  • Place of Presentation: Barcelona
  • Year and Date: 2011-02-05
• [Presentation] 強皮症患者におけるVEGFおよびHIF-1αの一塩基多型解析 (2010)
  • Author(s): 佐藤隆司、岡崎有佳、白井悠一郎、安岡秀剛、竹内勤、桑名正隆
  • Organizer: 第54回日本リウマチ学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2010-04-24
• [Presentation] 強皮症における循環血管内皮前駆細胞(EPC)数の再検討 (2010)
  • Author(s): 岡崎有佳、佐藤隆司、安岡秀剛、竹内勤、桑名正隆
  • Organizer: 第54回日本リウマチ学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2010-04-24
• [Presentation] 強皮症患者の抗トポイソメラーゼI抗体産生はいつからみられるか? (2010)
  • Author(s): 桑名正隆、鏑木淳一
  • Organizer: 第54回日本リウマチ学会総会
  • Place of Presentation: 神戸ポートピアホテル(神戸市)
  • Year and Date: 2010-04-24
• [Presentation] The gene polymorphism within hepatocyte growth factor promoter controls progression of systemic sclerosis-associated interstitial lung disease. (2010)
  • Author(s): Satoh T, Hoshino K, Kuwana M
  • Organizer: 1st Systemic Sclerosis World Congress
  • Place of Presentation: Florence
  • Year and Date: 2010-02-13
• [Presentation] Clinical and immunological characteristics of Japanese patients with connective tissue disease and pulmonary arterial hypertension (2010)
  • Author(s): Shirai Y, Yasuoka H, Takeuchi T, Satoh T, Kuwana M
  • Organizer: 1st Systemic Sclerosis World Congress
  • Place of Presentation: Florence
  • Year and Date: 2010-02-13
• [Presentation] Quantification of circulating endothelial progenitor cells verification of the EUSTAR recommendations. (2010)
  • Author(s): Okazaki Y, Satoh T, Yasuoka H, Kuwana M
  • Organizer: 1st Systemic Sclerosis World Congress
  • Place of Presentation: Florence
  • Year and Date: 2010-02-13
• [Presentation] Upregulated expression of versican in monocytes from patients with systemic sclerosis : role in amplification of MCP-1 activity at site of fibrosis. (2010)
  • Author(s): Yasuoka H, Masuda A, Yamaguchi Y, Satoh T, Kuwana M
  • Organizer: 1st Systemic Sclerosis World Congress
  • Place of Presentation: Florence
  • Year and Date: 2010-02-12
• [Presentation] 膠原病関連肺高血圧症 (2009)
  • Author(s): 桑名正隆
  • Organizer: 第59回日本アレルギー学会秋季学術大会
  • Place of Presentation: 秋田ビューホテル(秋田県)
  • Year and Date: 2009-10-29
• [Book] 全身性硬化症(強皮症).間質性肺疾患診療マニュアル (2010)
  • Author(s): 桑名正隆
  • Publisher: 南江堂
• [Book] 強皮症.最新内科学
  • Author(s): 桑名正隆
  • Publisher: 西村書店、東京(印刷中)