Enhancement of the cell therapeutic potency using low-molecular weight heparin protamine complex

• Project/Area Number: 26861052
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Dokkyo Medical University
• Principal Investigator: Kishimoto Satoko 獨協医科大学, 医学部, 助教 (10511488)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 再生医療 / 細胞移植 / 脂肪由来間質細胞 / 細胞キャリア / 下部尿路障害 / 腹圧性尿失禁 / サイトカイン

Outline of Final Research Achievements

Fragmin/Protamine Nano-Particles (F/P NPs) are recently developed as low-molecular weight, biodegradable carriers for adipose-derived stromal cells (ASCs). We examined the ability of ASCs/F/P NPs aggregates to rescue limb loss in a mouse model of hindlimb ischemia and increase in urethral resistance in a rat model of vaginal distention.
The F/P NPs augmented the effects of ASCs on angiogenesis and reversal of limb ischemia on postoperative days 7 and 14. Leak point pressure (LPP) decreased after vaginal distension (VD) and was recovered after the periurethral injection of ASCs and ASCs/F/P NPs aggregates of 7 and 14 days after VD treatment.

Research Products

• [Journal Article] Low-molecular weight heparin protamine complex augmented the potential of adipose-derived stromal cells to ameliorate limb ischemia (2016)
  • Author(s): Satoko Kishimoto, Ken-ichi Inoue, Shingo Nakamura, Hidemi Hattori, Masayuki Ishihara, Masashi Sakuma, Shigeru Toyoda, Hideki Iwaguro, Isao Taguchi, Teruo Inoue, Ken-ichiro Yoshida
  • Journal Title: Atherosclerosis Volume: 249 Pages: 132-139
  • DOI: 10.1016/j.atherosclerosis.2016.04.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Synergistic Cooperation of Heterogeneous Stromal Cells for Wound Healing (2017)
  • Author(s): 井上健一, 岸本聡子, 佐久間理吏, 豊田茂, 井上晃男
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 石川県立音楽堂他（金沢）
  • Year and Date: 2017-03-17
• [Presentation] 尿道括約筋断裂による腹圧性尿失禁ラットモデルを用いた脂肪由来間質細胞の移植効果の検討 (2016)
  • Author(s): 井上健一、山西友典、岸本聡子、井上晃男、吉田謙一郎
  • Organizer: 日本再生医療学会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2016-03-17
• [Presentation] Low-molecular weight heparin protamine complex augmented the potential of adipose-derived stromal cells to ameliorate limb ischemia (2015)
  • Author(s): 井上健一、岸本聡子、佐久間理吏、豊田 茂、田口 功、井上晃男、吉田謙一郎
  • Organizer: 獨協医学会
  • Place of Presentation: 獨協医科大学（栃木県下都賀郡壬生町）
  • Year and Date: 2015-12-05
• [Presentation] Nanoparticles of Heparin and Protamine Complex Augment the Potential for Adipose-derived Stromal Cells to Ameliorate Limb Ischemia (2015)
  • Author(s): 岸本聡子、井上健一、佐久間理吏、豊田茂、田口功、井上晃男
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] ラットにおける陰部神経切断モデルと膣過伸展モデルの腹圧下尿漏出時圧における比較検討 (2014)
  • Author(s): 山西友典、加賀勘家、内山智之、柴田千晴、岸本聡子、井上健一
  • Organizer: 第7回排尿障害モデル動物研究会
  • Place of Presentation: グランディエールブケトーカイ（静岡県静岡市）
  • Year and Date: 2014-12-05