Regenerative pancreatic islet transplantation for the young onset Type I diabetes mellitus. It is xenotransplantation of the pancreatic islet cell sheet.

• Project/Area Number: 23591871
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Fukushima Medical University
• Principal Investigator: ISHII Show 福島県立医科大学, 医学部, 助教 (40468129)
• Co-Investigator(Kenkyū-buntansha): ISE Kazuya 公立大学法人福島県立医科大学, 医学部, 講師 (90363746) ; SHIIZU Hirofumi 公立大学法人福島県立医科大学, 医学部, 助教 (70553709)
• Co-Investigator(Renkei-kenkyūsha): GOTOH Mitsukazu 公立大学法人福島県立医科大学, 医学部, 教授 (50162160)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 細胞シート / I型糖尿病 / 膵島移植 / 膵島再生 / ティッシュエンジニアリング / 異種移植 / 組織工学

Research Abstract

The present study was conducted to develop a dispersed islet cell-based tissue engineering approach for the treatment of diabetes mellitus. Dispersed islet cells obtained from rats were then plated on the laminin-5-PIPAAm dishes. At day 2 of culture, cultured islet cells were harvested as a uniformly connected tissue sheet by lowering the culture temperature from 37 degrees C to 20 degrees C for 30 min. Two harvested islet cell sheets were transplanted for engineering neo-islet tissues in the subcutaneous site of streptozotocin-induced diabetic mice. The diabetic mice that received islet sheet transplantation did not revert from hyperglycemia. Histological examination revealed that the transplanted islet cell sheets formed clusters of islet tissues and inflammatory cell infiltration. The present study may describe a new proof-of-concept therapeutic approach to engineer functional neo-islet tissues for xenotransplantation.

Research Products

• [Journal Article] Topographical arrangement of α- and β-cells within neo-islet tissues engineered by islet cell sheet transplantation in mice. (2013)
  • Author(s): Shimizu H, Ohashi K, Saito T, Utoh R, Ise K, Yamato M, Okano T, Gotoh M.
  • Journal Title: Transplantation Proceedings Volume: 45 Issue: 5 Pages: 1881-1884
  • DOI: 10.1016/j.transproceed.2013.01.003
  • Peer Reviewed
• [Journal Article] Preservation of pancreatic islets in cold UW solution Preservation of pancreatic islets in cold UW solution (2012)
  • Author(s): Ishii S, Saito T, Ise K, Yamashita M, Sato Y, Saito T, Tsukada M, Oshibe I, Kenjo A, Kimura T, Anazawa T, Suzuki S, Gotoh M
  • Journal Title: Islets Volume: 4(1) Issue: 1 Pages: 32-39
  • DOI: 10.4161/isl.18607
  • Peer Reviewed
• [Journal Article] Reversal of Diabetes by the Creation of Neo-islet Tissues into a Subcutaneous Site Using Islet Cell Sheets (2011)
  • Author(s): Saito T, Ohashi K, Utoh R, Shimizu H, Ise K, Suzuki H, Yamato M, Okano T, Gotoh M
  • Journal Title: Transplantation Volume: 29(11) Pages: 1231-6
• [Journal Article] Reversal of diabetes by the creation of neo-islet tissues into a subcuta- neous site using islet cell sheets. (2011)
  • Author(s): Saito Takahiro, Ohasi K, Uto R,Shimizu H, Ise K, Suzuki H, Yamato M, Okano M Gotoh M
  • Journal Title: Transplantation Volume: 92(11) Pages: 1231-1236
  • Peer Reviewed
• [Presentation] Long-term outcome of clinical islet transplantation using donors after cardiac death : a multicenter experience in Japan (2013)
  • Author(s): Anazawa T, Kenjo A, Kimura T, Ise K, Haga J, Sato N, Tsuchiya T, Sato T, Gotoh M
  • Organizer: The 14th World congress of the international pancreas and islet transplantation association
  • Place of Presentation: Monterey, CA, US
• [Presentation] Reassembly of alpha and beta cells of neo-islet tissues engineered in the subcutaneas space by islet-cell sheet transplantation in mice (2013)
  • Author(s): Shimizu H, Utoh R, Hanayama H, Ise K, Yamato M, Okano T, Gotoh M
  • Organizer: The 14th World congress of the international pancreas and islet transplantation association
  • Place of Presentation: Monterey, CA, US
• [Presentation] Adenoviral vector-megiated anti-apoptptic gene transduction for engineering functional islet cell sheets (2013)
  • Author(s): Hanayama H, Ohashi K, Utoh R, Ise K, Shimizu T, Yamato M, Mizuguchi H, Sakurai F, Okano T, Gotoh M
  • Organizer: The 14th World congress of the international pancreas and islet transplantation association
  • Place of Presentation: Monterey, CA, US
• [Presentation] Long-term follow-up of clinical islet transplantation using donors after cardiac death report of Japan islet transplantation registry (2013)
  • Author(s): Anazawa T, Kenjo A, Kimura T, Ise K, Haga J, Sato N, Tsuchiya T, Sato T, Gotoh M
  • Organizer: The 13th congress of the Asian society of transplantation
  • Place of Presentation: 京都
• [Presentation] 再生医学研究が変える膵島移植医療の近未来 (2013)
  • Author(s): 穴澤貴行、土屋貴男、見城明、伊勢一哉、木村隆、芳賀淳一郎、佐藤直哉、後藤満一
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡
• [Presentation] Long-term follow-up of clinical islet transplantation using donors after cardiac death: Report of the Japan Islet Transplantation Registry. (2013)
  • Author(s): Anazawa T, Kenjo A, Kimura T, Ise K, Haga J, Sato N, Tsuchiya T, Saito T, Gotoh M.
  • Organizer: The 13th Congress of the Asian Society of Transplantation
  • Place of Presentation: Kyoto Japan
• [Presentation] Long-term outcomes of clinical islet transplantation using donors after cardiac death: A multicenter experience in Japan. (2013)
  • Author(s): Anazawa T, Kenjo A, Kimura T, Ise K, Haga J, Sato N, Tsuchiya T, Saito T, Gotoh M.
  • Organizer: The 14th World congress of the International pancreas and islet transplantation association
  • Place of Presentation: Monterey, CA, USA
• [Presentation] Adenoviral vector-mediated anti-apoptotic gene transduction for engineering functional islet cell sheets. (2013)
  • Author(s): Hanayama H, Ohashi K, Utoh R, Ise K, Shimizu T, Yamato M, Mizuguchi H, Sakurai F, Okano T, Gotoh M.
  • Organizer: The 14th World congress of the International pancreas and islet transplantation association
  • Place of Presentation: Monterey, CA, USA
• [Presentation] Reassembly of alpha and beta cells of neo-islet tissues engineered in the subcutaneous space by islet-cell sheet transplantation in mice. (2013)
  • Author(s): Shimizu H, Utoh R, Hanayama H, Ise K, Yamato M, Okano T, Gotoh M.
  • Organizer: The 14th World congress of the International pancreas and islet transplantation association
  • Place of Presentation: Monterey, CA, USA
• [Presentation] 再生医学研究が変える膵島移植医療の近未来． (2013)
  • Author(s): 穴澤貴行、土屋貴男、見城 明、伊勢一哉、木村 隆、芳賀淳一郎、佐藤直哉、後藤満一．
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
• [Presentation] 膵島移植の新たな展開 (2011)
  • Author(s): 清水裕史、大橋一夫、斎藤敬弘、鵜頭理恵、伊勢一哉、大和雅之、岡野光夫、後藤満一
  • Organizer: 第36回日本外科系連合会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2011-06-16
• [Presentation] Functional islet tissue engineering is subcutaneous site using fabricated islet cell sheets (2011)
  • Author(s): Shimizu H, Ohashi K, Saito T, Utoh R, Ise K, Yamato M, Okano T, Gotoh M
  • Organizer: The 13th World congress of international pancreas and islet transplantation association
  • Place of Presentation: Prague, Czech Republic
  • Year and Date: 2011-06-03
• [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, 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
  • Year and Date: 2011-06-03
• [Presentation] Functional islet tissue engineering in subcutaneoua site using fabricated islet cell sheets. (2011)
  • Author(s): Shimizu H, Ohasi K, Saito Ta- kahiro, Uto R, Ise K, Yamato M, Okano M, Gotoh M
  • Organizer: The 13th World Congress of International pancreas and islettransplantation 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 Takaharu, Anaza-wa T, Tsuchiya T, Kenjo A, Sa- to S, Sato N, Saito Takuro, Ise K, Yamamoto M, Waguri S, Go-toh M
  • Organizer: The 13th World Congress of International pancreas and islettransplantation association
  • Place of Presentation: Prague. Czech Republic
• [Presentation] 膵島移植の新たな展開 －膵島細胞シートの開発－ (2011)
  • Author(s): 清水裕史，大橋一夫，齋藤敬弘，鵜頭理恵，伊勢一哉，大和雅之，岡野光夫，後藤満一
  • Organizer: 第36回日本外科系連合学会学術集会
  • Place of Presentation: ヒルトン東京ベイ（千葉県）
• [Book] 再生医療叢書5,代謝系臓器 (2012)
  • Author(s): 伊勢一哉
  • Publisher: 朝倉書店