Human Umbilical Cord Blood-derived Mononuclear Cell Transplantation Improves Pulmonary Arterial Hypertension in Immunodeficiency Mouse

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390392
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: The University of Tokushima
• Principal Investigator: KITAGWA Tetsuya 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (80240886)
• Co-Investigator(Kenkyū-buntansha): KITAICHI Takashi 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (20335813) ; NAKAGAWA Ryuji 徳島大学, 病院, 助教 (10403685) ; MAEDA Kazutoshi 徳島大学, 病院, 准教授 (30294680) ; SUGANO Mikio 徳島大学, 病院, 特任助教 (70563807) ; KANBARA Tamotsu 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (20380082) ; KUROBE Hirotsugu 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (30380083) ; YOSHIDA Homare 徳島大学, 病院, 助教 (50448338)
• Project Period (FY): 2009 – 2011
• Keywords: 臍帯血 / 細胞移植 / 未熟肺血管床

Research Abstract

Backgrounds and Objectives. The purpose of this study is to investigate whether human umbilical cord blood-derived mononuclear cell(hUCB-MNC) transplantation improves the development of pulmonary arterial hypertension(PAH) in monocrotaline(MCT)-treated mice. HUCB-MNC transplantation may have a new therapeutic potential for several congenital heart defects with primitive pulmonary vasculatures. Methods. MCT-induced PAH model was made using BALB/ c Slc-nu immunodeficiency mouse. HUCB-MNCs were adjusted to 1 x 107/ 0. 25 mL of concentration, and injected intravenously into those mice 4 weeks after MCT administration. The mice were divided into five groups :(1) vehicle-injected mice ;(2) MCT-treated mice ;(3) hUCB-MNC transplantation for PAH mice ;(4) hUCB-MNC+ plasma transplantation for PAH mice ;(5) plasma transplantation for PAH mice. Assessment of PAH were performed by the ratio of right ventricular to ventricular septum plus left ventricular weight(RV/ S+ LV), medial thickness of small pulmonary arteries, and pulmonary acceleration time/ ejection time(PAT/ ET) of the main pulmonary artery by echocardiography. Results. RV/ S+ LV ratio, medial thickness of small pulmonary arteries and PAT/ ET were significantly improved by hUCB-MNC transplantation with or without plasma, respectively. Conclusions. Our data shows that hUCB-MNC transplantation improves MCT-induced PAH and its efficacy is dependent on hUCB-MNCs themselves

Research Products

• [Journal Article] Autologous Peripheral Blood-Derived Mononuclear Cells Autologous Peripheral Blood-Derived Mononuclear Cells Induced by Erythropoietin Improve Critical Ischemic Limbs (2012)
  • Author(s): Kanbara T, Kurobe T, Kitaichi T, Sugano M, Nakayama T, Kinoshita H, Iwase T, Akaike M, Abe M, Sata M, Matsumoto T, Kitagawa T
  • Journal Title: Annals of Vascular Diseases Volume: 5(1) Pages: 52-60
  • Peer Reviewed
• [Journal Article] Human cord-blood cell transplantation to monocrotaline-induced pulmonary arterial hypertension in mice (2011)
  • Author(s): Sugano M, Kurobe H, Hirata Y, Nakagawa R, Yoshida H, Kitaichi T, Nakayama T, Kinoshita H, Motoki T, Kanbara T, Sugasawa N, Miki M, Maeda K, Sata M, Kitagawa T
  • Journal Title: Gen Thorac Cardiovasc Surg Volume: 59 Pages: 213
  • Peer Reviewed
• [Journal Article] Functional restoration of endothelial cells of the cryopreserved heart valve (2011)
  • Author(s): Fujimoto E, Yoshizumi M, Kanbara T, Kurobe H, Motoki T, Sugano M, Nakayama T, Kitaichi T, Kitagawa T
  • Journal Title: Gen Thorac Cardiovasc Surg Volume: 59(3) Pages: 169-74
  • Peer Reviewed
• [Journal Article] Enhanced inflammation in epicardial fat in patients with coronary artery disease (2011)
  • Author(s): Hirata Y, Kurobe H, Akaike M, Chikugo F, Hori T, Bando Y, Nishio C, Nakaya Y, Kitagawa T, Sata M
  • Journal Title: Int Heart J Volume: 52(3) Pages: 139-42
  • Peer Reviewed
• [Journal Article] Coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue (2011)
  • Author(s): Hirata Y, Tabata M, KurobeH, Motoki T, Akaike M, Nishio C, Higashida M, Mikasa H, Nakaya Y, Takanashi S, Igarashi T, Kitagawa T, Sata M
  • Journal Title: J Am Coll Cardiol Volume: 58(3) Pages: 248-55
  • Peer Reviewed
• [Journal Article] Ezetimibe monotherapy ameliorates vascular function in patients with hypercholesterolemia through decreasing oxidative stress (2011)
  • Author(s): Kurobe H, Aihara K, Higashida M, Hirata Y, Nishiya M, Matsuoka Y, Kanbara T, Nakayama T, Kinoshita H, Sugano M, Fujimoto E, Kurobe A, Sugasawa N, Kitaichi T, Akaike M, Sata M, Matsumoto T, Kitagawa T
  • Journal Title: J Atheroscler Thromb Volume: 18(12) Pages: 1080-9
  • Peer Reviewed
• [Journal Article] Undiminished regulatory T cells in the thymus of patients with myasthenia gravis (2010)
  • Author(s): Matsui N, Nakane S, Saito F, Ohigashi I, Nakagawa Y, Kurobe H, Takizawa H, Mitsui T, Kondo K, Kitagawa T, Takahama Y, Kaji R
  • Journal Title: Neurology Volume: 74(10) Pages: 816-20
  • Peer Reviewed
• [Journal Article] LETTERS TO THE EDITOR : Optimal surgical approach for repair of aortopulmonary window with aortic origin the right pulmonary artery (2010)
  • Author(s): Kitagawa T, Kitaichi T, Yoshida H
  • Journal Title: J Thorac Cardiovasc Surg Volume: 139(1) Pages: 238-239
  • Peer Reviewed
• [Journal Article] Assessment of systemic-pulmonary collateral arteries in children with cyanotic congenital heart disease using multidetector-row computed tomography : Comparison with conventional (2010)
  • Author(s): Hayabychi Y, Inoue M, Watanabe N, Sakata M, Nabo MM, Kitagawa T, Kitaichi T, Kagami S
  • Journal Title: Int J Cardiol Volume: 138(3) Pages: 266-271
  • Peer Reviewed
• [Journal Article] Role of Hif-1αin T cells as a negative regulator in development of vascular remodeling (2010)
  • Author(s): Kurobe H, Urata M, Ueno M, Ono S, Izawa-Ishizawa Y, Fukuhara Y, Gukuhara Y, Yu L, Ripen AM, Kanbara T, Aihara K, Ishizawa K, Akaike M, Gonzalez FJ, Tamaki T, Takahama Y, Yoshizumi M, Kitagawa T, Tomita S
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology Volume: 30(2) Pages: 210-7
  • Peer Reviewed
• [Journal Article] Syngeneic bone marrow mononuclear cells improve pulmonary arterial hypertension through vascular endothelial growth factor upregulation (2009)
  • Author(s): Yoshida H, Kitaichi T, Urata M, Kurobe H, Kanbara T, Motoki T, Kitagawa T
  • Journal Title: Annals of Thoracic Surgery Volume: 88(2) Pages: 418-24
  • Peer Reviewed
• [Presentation] 肺高血圧症に対するヒト臍帯血細胞移植治療の可能性 (2011)
  • Author(s): 菅野幹雄、黒部裕嗣、平田陽一郎、中川竜二、吉田誉、北市隆、中山泰介、木下肇、元木達夫、神原保、菅澤典子、三木美枝、前田和寿、佐田政隆、北川哲也
  • Organizer: 第64回日本胸部外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20111009-12