New Strategy for the Treatment of Fracture Nonunion with CD34-positive Cell Transplantation

• Project/Area Number: 25462331
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kobe University
• Principal Investigator: Matsumoto Tomoyuki 神戸大学, 医学部附属病院, 助教 (50546588)
• Co-Investigator(Kenkyū-buntansha): MATSUSHITA Takehiko 神戸大学, 医学部付属病院, 助教 (40467650) ; KURODA Ryosuke 神戸大学, 医学(系)研究科(研究院), 准教授 (80379362) ; KUROSAKA Masahiro 神戸大学, 医学(系)研究科(研究院), 教授 (70170115)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: CD34陽性細胞 / 偽関節 / 幹細胞 / 骨折 / 臨床試験

Outline of Final Research Achievements

Phase 1/2 Clinical trial of CD34-positive cell transplantation for patients with fracture nonunion was successfully performed. However, more effective way should be explored. Therefore, we examined 2 new strategies for this treatment. The first results proved that transplantation of AteloGene with Lnk si RNA contributed to ealry healing of mouse fracture model.
The second results proved that ex-vivo expanded CD34-positive cells with key growth factors improved the efficacy by in vitro expansion culture and in vivo xenotransplantation model (human cell-immunodeficient rat).

Research Products

• [Journal Article] SDF-1/CXCR4 Axis in Tie2-lineage Cells Including Endothelial Progenitor Cells Contributes to Bone Fracture Healing. (2015)
  • Author(s): Kawakami Y, Ii M, Matsumoto T, Kuroda R, Kuroda T, Kwon SM, Kawamoto A, Akimaru H, Mifune Y, Shoji T, Fukui T, Kurosaka M, Asahara T.
  • Journal Title: J Bone Miner Res. Volume: 30(1) Issue: 1 Pages: 95-105
  • DOI: 10.1002/jbmr.2318
  • Peer Reviewed
• [Journal Article] Superior Potential of CD34-Positive Cells Compared to Total Mononuclear Cells for Healing of Nonunion Following Bone Fracture. (2015)
  • Author(s): Fukui T, Mifune Y, Matsumoto T, Shoji T, Kawakami Y, Kawamoto A, Ii M, Akimaru H, Kuroda T, Horii M, Yokoyama A, Alev C, Kuroda R, Kurosaka M, Asahara T.
  • Journal Title: Cell Transplant Volume: 24(7) Issue: 7 Pages: 1379-93
  • DOI: 10.3727/096368914x681586
  • Peer Reviewed
• [Journal Article] A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization (2013)
  • Author(s): Kawakami Y, Ii M, Matsumoto T, Kawamoto A, Kuroda R, Akimaru H, Mifune Y, Shoji T, Fukui T, Asahi M, Kurosaka M, Asahara T.
  • Journal Title: Laboratory Investigation Volume: 93 Issue: 9 Pages: 1036-1053
  • DOI: 10.1038/labinvest.2013.93
  • Peer Reviewed
• [Journal Article] Clinical Impact of Circulating CD34-positive Cells on Bone Regeneration and Healing. (2013)
  • Author(s): Kuroda R, Matsumoto T, Kawakami Y, Fukui T, Mifune Y, Kurosaka M.
  • Journal Title: Tissue Engineering Part B Volume: Epub
  • Peer Reviewed
• [Journal Article] 末梢血CD34陽性細胞移植による難治性骨折治療． (2013)
  • Author(s): 松本知之、新倉隆宏、黒田良祐．
  • Journal Title: Pharma Medica Volume: 31 (4) Pages: 9-13
  • Peer Reviewed
• [Presentation] 偽関節患者を対象とした、自家末梢血CD34陽性細胞を用いた骨・血管再生療法． (2014)
  • Author(s): 松本知之，新倉隆宏，川上洋平，福井友章，美舩泰，李相亮，川本篤彦，黒坂昌弘，浅原孝之，黒田良祐
  • Organizer: 第11回日本再生医療学会
  • Place of Presentation: 京都
  • Invited
• [Presentation] 偽関節患者を対象とした、自家末梢血CD34陽性細胞を用いた骨・血管再生療法に関する第I・II相臨床試験． (2013)
  • Author(s): 松本知之，新倉隆宏，川上洋平，福井友章，美舩泰，李相亮，川本篤彦，黒坂昌弘，浅原孝之，黒田良祐
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 千葉
  • Invited
• [Book] Stem Cells and Bone Tissue (2013)
  • Author(s): Matsumoto T, Asahara T
  • Publisher: Science Publishers CRC Press