Optimization of collagenase activity and regulation of ion channel associated with cell viability for improving pancreatic islet transplantation

• Project/Area Number: 23791554
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Fukushima Medical University
• Principal Investigator: ANAZAWA Takayuki 福島県立医科大学, 医学部, 助教 (90566811)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 膵島移植 / 膵島分離 / 糖尿病 / イオンチャネル / 移植・再生医療 / 外科学 / 細胞・組織

Research Abstract

Protection of pancreatic islets during isolation procedures andmaximization of islet yield are mandatory for successful islet transplantation. An enzyme mixture composed of neutral protease with high intact class I collagenase recovered higher islet yield from both rat and human pancreas. Our results also indicated that Clinflux into the cells causes the cell damage during the digestion procedure. Inhibition of Clinflux into islets by Clchannel inhibitor or Cl--free condition protects islets in both heart-beating and non-heart-beating donor model, offering a new strategy for improving human islet isolation outcome.

Research Products

• [Journal Article] A new enzyme mixture to increase the yield and transplant rate of autologous and allogeneic human islet product (2012)
  • Author(s): （Balamurugan AN） Takayuki Anazawa
  • Journal Title: Transplantation Volume: 93 Issue: 7 Pages: 693-702
  • DOI: 10.1097/tp.0b013e318247281b
  • Peer Reviewed
• [Journal Article] Mitomycin-C treatment significantly reduces central damage of islets in culture (2012)
  • Author(s): Saito T, Saito T, Sato Y, Ise K, Anazawa T, Oshibe I, Haga J, Yamamoto M, Waguri S, Gotoh M.
  • Journal Title: Pancreas. Volume: 41(2) Issue: 2 Pages: 245-252
  • DOI: 10.1097/mpa.0b013e31822461c7
  • Peer Reviewed
• [Journal Article] 膵島移植症例登録報告（2011） (2012)
  • Author(s): 穴澤 貴行
  • Journal Title: 移植 Volume: 47 Pages: 443-449
  • NAID: 10030209416
• [Journal Article] Improved islet yield and function by use of a chloride channel blocker during collagenase digestion. (2011)
  • Author(s): Anazawa T, Sato Y, Saito T, Tsuchiya T, Kenjo A, Kimura T, Haga J, Miyake M, Waguri S, Hazama A, Gotoh M.
  • Journal Title: Transplantation Volume: 92(8) Issue: 8 Pages: 871-877
  • DOI: 10.1097/tp.0b013e31822e6eb4
  • Peer Reviewed
• [Journal Article] Prediction of pancreatic tissue densities by an analytical test gradient system before purification maximizes human islet recovery for isletautotransplantation/allotransplantation (2011)
  • Author(s): Anazawa T, Matsumoto S, Yonekawa Y, Loganathan G, Wilhelm JJ, Soltani SM, Papas KK, Sutherland DE, Hering BJ, Balamurugan AN
  • Journal Title: Transplantation Volume: 91(5) Issue: 5 Pages: 508-514
  • DOI: 10.1097/tp.0b013e3182066ecb
  • Peer Reviewed
• [Presentation] 先進的組織細胞移植医療発展の先駆的モデルとしての膵島移植臨床開発:その展望と課題 (2012)
  • Author(s): 穴澤貴行, 土屋貴男, 見城 明, 伊勢一哉, 齋藤拓朗, 後藤満一
  • Organizer: 第11回日本組織移植学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-08-04
• [Presentation] Disappeared islet graft after intraportal transplantation in the recipient suffered from recurrent sepsis (2012)
  • Author(s): Anazawa T, Tsuchiya T, Kenjo A, Haga J, Sato T, Sato N, Ise K, Saito T,Tasaki K, Gotoh M
  • Organizer: 24th International Congress of the Transplantation Society
  • Place of Presentation: Berlin, Germany
• [Presentation] 膵島移植の現状と今後の展望 (2012)
  • Author(s): 穴澤貴行, 土屋貴男, 見城 明, 伊勢一哉, 芳賀淳一郎, 齋藤拓朗, 後藤満一
  • Organizer: 第48回日本移植学会総会
  • Place of Presentation: 名古屋
• [Presentation] Disappeared islet graft after intraportal transplantation in the recipient suffered from recurrent sepsis (2012)
  • Author(s): Takayuki Anazawa
  • Organizer: 24th International Congress of The Transplantation Society
  • Place of Presentation: Berlin, Germany
• [Presentation] Inhibition of chloride ion influx into islet cells protects islets during pancreatic islet isolation (2011)
  • Author(s): Anazawa T, Tsuchiya T, Kenjo A, Haga J, Sato T, Sato N, Saito T, Sato Y, Miyake M, Hazama A, Gotoh M
  • Organizer: The 13th World congress of International pancreas and islet transplantation association
  • Place of Presentation: Prague, Czech Republic
• [Presentation] Predicting porcine islet yield by acute C-peptide response to arginine stimulation of donor pigs and pancreas dithizone scoring system. (2011)
  • Author(s): Anazawa T, Graham M, Abouaish J, Loganathan G, Hering BJ, A.N. Balamurugan
  • Organizer: The 13th World congress of International pancreas and islet transplantation association
  • Place of Presentation: Prague, Czech Republic.
• [Presentation] Mitomycin-C treatment protects islets from the progression of central damage during culture. (2011)
  • Author(s): Haga J, Saito T, Anazawa T, Tsuchiya T, Kenjo A, Sato S, Sato N, Saito T, Ise K, Yamamoto M, Waguri S, Gotoh M
  • Organizer: The 13th World congress of International pancreas and islet transplantation association
  • Place of Presentation: Prague, Czech Republic
• [Presentation] Cl-チャネル阻害による細胞保護効果の膵島分離への応用-臨床膵島移植確立への細胞生理学的アプローチ- (2011)
  • Author(s): 穴澤貴行, 土屋貴男, 見城 明, 芳賀淳一郎, 佐藤 哲, 三宅将生, 狹間章博, 後藤満一
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 東京
• [Presentation] 重症低血糖発作を伴うインスリン依存性糖尿病に対する心停止ドナーからの膵島移植:日本膵・膵島移植研究会事務局報告 (2011)
  • Author(s): 穴澤貴行, 土屋貴男, 伊勢一哉, 見城明, 齋藤拓朗, 後藤満一
  • Organizer: 第47回日本移植学会総会
  • Place of Presentation: 仙台
• [Presentation] Inhibition of chloride ion influx into islet cells protects islets during pancreatic islet isolation (2011)
  • Author(s): Takayuki Anazawa
  • Organizer: 13th World congress of International pancreas and islet transplantation association
  • Place of Presentation: チェコ・プラハ
• [Presentation] 先進的組織細胞移植医療発展の先駆的モデルとしての膵島移植臨床開発：その展望と課題
  • Author(s): 穴澤 貴行
  • Organizer: 第11回日本組織移植学会学術集会
  • Place of Presentation: 東京
• [Patent(Industrial Property Rights)] 細胞分離用酵素溶液及び細胞分離方法、並びに膵島分離方法 (2013)
  • Inventor(s): 穴澤貴行
  • Industrial Property Rights Holder: 穴澤貴行、狹間章博、後藤満一
  • Filing Date: 2013-01-29
  • Overseas