Investigation of human vascular development and aging using human ES/iPS cells

• Project/Area Number: 21790721
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto University
• Principal Investigator: SONE Masakatsu Kyoto University, 医学研究科, 助教 (40437207)
• Research Collaborator: TAURA Daisuke , 日本学術振興会特別研究員(PD) ; HOMMA Koichiro 京都大学, 医学研究科, 客員研究員 ; SUZUKI Yutaka NPO法人幹細胞創薬研究所
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 血管 / 再生 / ES / iPS / 分化 / 老化 / 分子血管病怠学 / 内分泌学 / 循環器病学 / iPS細胞 / 抗加齢医学

Research Abstract

We succeeded in inducing iPS cells to differentiate into vascular endothelial cells (ECs) and mural cells (MCs), which we were able to isolate. We also established a feeder- and serum-free method that enables us to more efficiently induce ECs. Human ES-derived ECs (ESECs) and iPS-derived ECs (iPSECs) had a greater potential for wound re-endothelialization and tube formation than human adult ECs (HAECs) in vitro. Next we carried out a gene expression analysis of these three types of ECs using gene chip technology. The expression level of Sirt1, an aging-related gene that encodes a NAD-dependent histone deacetylase, was higher in ESECs/iPSECs than in HAECs. When Sirt1 activity was knocked down by siRNA or inhibited by a specific Sirt1 antagonist, the aforementioned differences in the cellular functionality were abolished, which suggests that differences in Sirt1 activity contribute to the observed differences in the cellular functionality.

Research Products

• [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 Pages: 42-47
  • NAID: 120002598375
  • Peer Reviewed
• [Journal Article] Simple and highly efficient method for production of endothelial cells from human embryonic stem cells. (2010)
  • Author(s): Tatsumi R, Suzuki Y, Sumi T, Sone M, Suemori H, Nakatsuji N.
  • Journal Title: Cell Transplant.[Epub ahead of print] 22
  • 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, et al.
  • Journal Title: Atherosclerosis. Volume: Sep;212(1): Pages: 42-7
  • NAID: 120002598375
  • Peer Reviewed
• [Journal Article] Simple and highly efficient method for production of endothelial cells from human embryonic stem cells. (2010)
  • Author(s): Tatsumi R, Sone M, et al.
  • Journal Title: Cell Transplant. Volume: Dec 22.(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Induction and isolation of vascular cells from human induced pluripotent stem cells. (2009)
  • Author(s): Taura D, Sone M, Homma K, Oyamada N, Takahashi K, Tamura N, Yamanaka S, Nakao K.
  • Journal Title: Arterioscler Thromb Vasc Biol. 29(7) Pages: 1100-1103
  • Peer Reviewed
• [Journal Article] Induction and isolation of vascular cells from human induced pluripotent stem cells. (2009)
  • Author(s): Taura D, Sone M, et al.
  • Journal Title: Arterioscler Thromb Vasc Biol. 29 Pages: 1100-1103
  • Peer Reviewed
• [Journal Article] Adipogenic differentiation of human induced pluripotent stem cells : comparison with that of human embryonic stem cells. (2009)
  • Author(s): Taura D, Sone M, et al.
  • Journal Title: FEBS Lett. 583 Pages: 1029-1033
  • Peer Reviewed
• [Presentation] ヒトiPS/ESからの血管構成細胞分化誘導・単離技術の確立と疾患iPS研究への応用 (2011)
  • Author(s): 曽根正勝, 他
  • Organizer: 第10回日本再生医療学会総会
  • Place of Presentation: 東京、日本
  • Year and Date: 2011-03-02
• [Presentation] ヒトiPS/ESからの血管構成細胞分化誘導・単離技術の確立と疾患iPS研究への応用 (2011)
  • Author(s): 曽根正勝, 他
  • Organizer: 第10回日本再生医療学会総会
  • Place of Presentation: 東京(京王プラザホテル)(口演)
  • Year and Date: 2011-03-02
• [Presentation] 心血管ホルモンと幹細胞を用いた血管保護・再生治療の探索 (2010)
  • Author(s): 曽根正勝, 他
  • Organizer: 京都成人血管病シンポジウム
  • Place of Presentation: 京都(ブライトンホテル)
  • Year and Date: 2010-12-11
• [Presentation] The characteristic and potential of human ES and iPS -derived vascular cells. (2010)
  • Author(s): Masakatsu Sone, et al.
  • Organizer: 14th International Congress of Endocrinology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-03-28
• [Presentation] ヒトESおよびiPS細胞を用いたヒト血管分化・再生・老化機構の解明 (2010)
  • Author(s): 曽根正勝, 他
  • Organizer: 第9回日本再生医療学会総会
  • Place of Presentation: 広島、日本
  • Year and Date: 2010-03-18
• [Presentation] ヒトESおよびiPS細胞を用いたヒト血管分化・再生・老化機構の解明 (2010)
  • Author(s): 曽根正勝
  • Organizer: 第9回日本再生医療学会総会(口演)
  • Place of Presentation: 広島
  • Year and Date: 2010-03-18
• [Presentation] Induction and Isolation of Vascular Cells from Human ES and iPS cells : as a research tool for vascular biology (2009)
  • Author(s): Masakatsu Sone, Kazuwa Nakao
  • Organizer: 5th SEOUL Conference on Cardiovascular Research
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2009-10-31
• [Presentation] ヒトESおよびiPS細胞を用いたヒト血管保護・再生因子の探索 (2009)
  • Author(s): 曽根正勝, 他
  • Organizer: 第82回日本内分泌学会学術総会公募シンポジウム1
  • Place of Presentation: 前橋、日本
  • Year and Date: 2009-04-23
• [Presentation] ヒトESおよびiPS細胞を用いたヒト血管保護・再生因子の探索 (2009)
  • Author(s): 曽根正勝
  • Organizer: 第82回日本内分泌学会学術総会(シンポジウム)
  • Place of Presentation: 群馬
  • Year and Date: 2009-04-23