Establishment of novel cellular therapy for hemophilia A using autologous blood outgrowth endothelial progenitors

• Project/Area Number: 22790995
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Nara Medical University
• Principal Investigator: MATSUI Hideto 奈良県立医科大学, 医学部, 講師 (00571027)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 小児血液学 / 血友病A / 血管内皮前駆細胞 / レンチウイルスベクター / 遺伝子治療 / 細胞療法 / イヌモデル

Research Abstract

We have established ex vivo gene transfer system using genetically-modified blood outgrowth endothelial progenitor cells(BOECs) which are capable of synthesizing therapeutic levels of plasma FVIII over a prolonged time periods.^<20> Using this ex vivo gene transfer strategy, we can provide for the safe and efficacious delivery of FVIII following subcutaneous implantation of BOECs in hemophilia A mouse model. Now, we would like to try this strategy in hemophilia A dog model.

Research Products

• [Journal Article] Endothelial progenitor cell-based therapy for hemophilia A (2012)
  • Author(s): Matsui H
  • Journal Title: International Journal of Hematology Volume: 95(2) Pages: 119-124
  • NAID: 10030267050
• [Journal Article] microRNA制御レンチウイルスベクターによる肝臓特異的第VIII因子誘導:血友病Aインヒビターに対する新規免疫寛容導入アプローチ (2011)
  • Author(s): 松井英人
  • Journal Title: 日本血栓止血学会誌 Volume: 22(6) Pages: 377-383
• [Journal Article] A microRNA-regulated and GP64-pseudotyped lentiviral vectors mediated stable expression of FVIII in murine model of hemophilia A (2011)
  • Author(s): Matsui H, Hegadorn C, Ozelo M, Burnett E, Tuttle A, Labelle A, McCray PB Jr, Naldini L, Brown B, Hough C, Lillicrap D
  • Journal Title: Molecular Therapy Volume: 19(4) Pages: 723-730
• [Journal Article] microRNA制御レンチウイルスベクターによる肝臓特異的第VIII因子発現誘導:血友病Aインヒビターに対する新規免疫寛容導入アプローチ (2011)
  • Author(s): 松井英人
  • Journal Title: 日本血栓止血学会誌 Volume: 22(6) Pages: 377-383
  • NAID: 10031144656
  • Peer Reviewed
• [Journal Article] Characterization of viability and proliferation of alginate-poly-L-lysine alginate encapsulated myoblasts using flow cytometry (2010)
  • Author(s): Thakur A, Sengupta R, Matsui H, Lillicrap D, Jones K, Hortelano G
  • Journal Title: Journal of Biomedecal Material Research Volume: 94B(2) Pages: 296-304
• [Journal Article] Characterization of viability and proliferation of alginate-poly-L-lysine-alginate encapsulated myoblasts using flow cytometry. (2010)
  • Author(s): Thakur A, et.al.
  • Journal Title: Journal of Biomedical Materials Research B : Applied Biomaterials Volume: 94(2) Pages: 296-304
  • Peer Reviewed
• [Presentation] Immune tolerance induction to FVIII in hemophilia A using autologous endothelial progenitors (2011)
  • Author(s): Hideto Matsui, David Lillicrap, Mitsuhiko Sugimoto, Midori Shima
  • Organizer: The 2nd Meeting of Asian Cellular Therapy Organization
  • Place of Presentation: Miyazaki, Japan
  • Year and Date: 2011-10-19
• [Presentation] Immune tolerance induction to FVIII in hemophilia A using autologous endothelial progenitors (2011)
  • Author(s): Hideto Matsui, et.al.
  • Organizer: The 2^<nd> meeting of ACTO
  • Place of Presentation: Miyazaki, Japan
  • Year and Date: 2011-10-18
• [Presentation] 自己血管内皮前駆細胞移植による血友病Aインヒビターに対する新規免疫寛容導入療法 (2011)
  • Author(s): 松井英人、David Lillicrap、杉本充彦、嶋緑倫
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-16
• [Presentation] Stem cell-based gene therapy for hemophilia A (2011)
  • Author(s): Hideto Matsui
  • Organizer: The 7^<th> Aso International Meeting
  • Place of Presentation: Kumamoto, Japan
  • Year and Date: 2011-07-30
• [Presentation] Long-term phenotypic correction of hemophilia A mice following injection of miRNA-regulated lentiviral vectors (2010)
  • Author(s): Hideto Matsui, David Lillicrap, Mitsuhiko Sugimoto, Midori Shima
  • Organizer: 6^<th> Congress of the Asia Pacific Society on Thrombosis and Haemostasis
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2010-10-14
• [Presentation] Long-term phenotypic correction of hemophilia A mice following injection of miRNA-regulated lentiviral vectors. (2010)
  • Author(s): Matsui H, et.al.
  • Organizer: 6^<th> Congress of the Asia Pacific Society on Thrombosis and Haemostasis
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2010-10-14
• [Presentation] Sustained therapeutic levels of FVIII activity from lentivirally-engineered blood outgrowth endothelial cells requires cell stability and augmented angiogenesis (2010)
  • Author(s): Hideto Matsui, Margareth Ozelo, Andrea Labelle, Carol Hegadorn, Patrick Thompson, Erin Burnnet, Christine Hough, David Lillicrap
  • Organizer: The 13^<th> Annual Meeting of American Society of Gene and Cell Therapy
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2010-05-21
• [Presentation] Sustained therapeutic levels of FVIII activity from lentivirally-engineered blood outgrowth endothelial cells requires cells stability and augmented angiogenesis. (2010)
  • Author(s): Matsui H, et.al.
  • Organizer: The 13^<th> Annual Meeting of American Society of Gene and Cell Therapy
  • Place of Presentation: Washington DC, U.S.A
  • Year and Date: 2010-05-21
• [Presentation] 第VIII因子発現レンチウイルスベクターによる血友病Aインヒビターに対する新規免疫寛容療法 (2010)
  • Author(s): 松井英人, 杉本充彦, デービット・リリクラップ, 柴田優, 嶋緑倫
  • Organizer: 第33回日本血栓止血学会学術集会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2010-04-23