Insulin secretion ability construction due to hyper dimension of pancreatic islet cell sheet using the cellular engineering

• Project/Area Number: 22591412
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Fukushima Medical University
• Principal Investigator: ISE Kazuya 福島県立医科大学, 医学部, 講師 (90363746)
• Co-Investigator(Kenkyū-buntansha): YAMASHITA Michitoshi 福島県立医科大学, 医学部, 助教 (20381387) ; SAITO Takahiro 福島県立医科大学, 医学部, 博士研究員 (00566812) ; SHIMIZU Hirofumi 福島県立医科大学, 医学部, 助教 (70553709)
• Co-Investigator(Renkei-kenkyūsha): GOTOH Mitsukazu 福島県立医科大学, 医学部, 教授 (50162160)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: I 型糖尿病 / 膵島移植 / 膵島再生 / 細胞シート / ティッシュエンジニアリング / I型糖尿病

Research Abstract

Pancreatic islets were obtained from Lewis rats, and dissociated islet cells were obtained by incubating with trypsin-EDTA. Dissociated islet cells were then plated onto the PIPAAm dishes. After reaching confluency at day 2, islet cells were successfully harvested as a uniformly spread islet sheet by lowering the culture temperature. We then conducted islet sheet transplantation procedure to create neo-islet tissues into subcutaneous space of Streptozotocin-induced diabetic SCID mice. Histological analyses revealed that strip-shaped neo-islet tissues in the subcutaneous space. This neo-islet engineering approach successfully converted the hyperglycemia to euglycemia in all the recipients and sustained the therapeutic effects for 300 days (length of the experiments). We then conducted intra-peritoneal glucose tolerant tests to the recipients, and found that the recipient SCID mice showed glucose changes that are identical to normal mice

Research Products

• [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] Adenine nucleotide levels in a closed enzymatic digestion system for porcine islet isolation (2012)
  • Author(s): Oshibe I, Saito T, Sato Y, Saito T, Tsukada M, Ise K, Kenjo A, Kimura T, Anazawa T, Suzuki S, Hashimoto Y, Gotoh M
  • Journal Title: Cell Transplantation. Volume: 21(2-3) Issue: 2-3 Pages: 483-491
  • DOI: 10.3727/096368911x605394
  • 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) Pages: 245-52
  • Peer Reviewed
• [Journal Article] A model to evaluate toxic factors influencing islets during collagenase digestion: the role of serine protease inhibitor in the protection of islets. (2012)
  • Author(s): Tsukada M, Saito T, Ise K, Kenjo A, Kimura T, Satoh Y, Sai to T, Anazawa T, Oshibe I, Suzuki S, Hashimoto Y, Gotoh M
  • Journal Title: Cell Transplantation. Volume: 21(2-3) Issue: 2-3 Pages: 473-482
  • DOI: 10.3727/096368911x605385
  • Peer Reviewed
• [Journal Article] Mizoribine as Sole Immunosuppressive Agent in Islet Xenotransplantation Models: A Candidate Immunosuppressant Causing no Adverse Effects on Islets. (2012)
  • Author(s): Yamashita M, Saito T, Ise K, Ishii S, Satoh Y, Saito T, Oshibe I, Shimizu H, Kenjo A, Kimura T, Gotoh M.
  • Journal Title: Cell Transplantation Volume: 21(2-3) Issue: 2-3 Pages: 535-545
  • DOI: 10.3727/096368911x605457
  • 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] 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: 92(11) Issue: 11 Pages: 1231-1236
  • DOI: 10.1097/tp.0b013e3182375835
  • Peer Reviewed
• [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] 膵島細胞シートへのアデノウィルスベクターによるアポトーシス遺伝子導入に関する検討 (2013)
  • Author(s): 花山寛之,大橋一夫,鵜頭理恵, 伊勢一哉,櫻井文教,水口裕之,岡野光夫,後藤満一
  • Organizer: 第12回日本再生医療学会
  • Place of Presentation: 横浜
• [Presentation] アデノウィルスベクターを用いた抗アポトーシス遺伝子導入に関する検討-膵島細胞シートの移植効率向上を目指して- (2013)
  • Author(s): 花山寛之,大橋一夫,鵜頭理恵, 伊勢一哉,櫻井文教,水口裕之,岡野光夫,後藤満一
  • Organizer: 第12回日本再生医療学会
  • Place of Presentation: 横浜
• [Presentation] 膵島細胞シートへのアデノウィルスベクターによるアポトーシス遺伝子導入に関する検討． (2013)
  • Author(s): 花山寛之
  • Organizer: 第12回日本再生医療学会
  • Place of Presentation: 横浜
• [Presentation] アデノウィルスベクターを用いた抗アポトーシス遺伝子導入に関する検討―膵島細胞シートの移植効率向上を目指して― (2013)
  • Author(s): 花山寛之
  • Organizer: 第12回日本再生医療学会
  • Place of Presentation: 横浜
• [Presentation] Successful management of hepatic venous outflow obstruction in pediatric liver transplantation: A case report (2012)
  • Author(s): Haga J, Tsuchiya T, Kenjo A,KimuraT,Anazawa T,Sato T,Sato N,Ise K,Saito T,Gotoh M
  • Organizer: International Pediatric TransplantAssociation
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2012-09-23
• [Presentation] 膵島細胞シートの皮下移植における長期血糖制御能 (2012)
  • 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11回日本組織移植学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-08-04
• [Presentation] Sustained Therapeutic Effects of Neo-islet Tissue Engineering by IsletSheet Transplantation (2012)
  • Author(s): Shimizu H, Ohashi K, Saito T, Utoh R, Ise K, Yamato M, Okano T, Gotoh M.
  • Organizer: The 24th International Congress of The Transplantation Society
  • Place of Presentation: Berlin, Germany
• [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: The 24th International Congress of The Transplantation Society
  • Place of Presentation: Berlin, Germany
• [Presentation] 皮下膵島組織作製による糖尿病治療-300日の観察 (2012)
  • Author(s): 花山寛之,大橋一夫,齋藤敬弘,清水裕史,鵜頭理恵,伊勢一哉,岡野光夫,後藤満一
  • Organizer: 第11回日本再生医療学会
  • Place of Presentation: 横浜
• [Presentation] Disappeared islet graft after intraportal transplantation in the recipient suffered from recurrent sepsis. (2012)
  • Author(s): Anazawa T
  • Organizer: The 24th International Congress of The Transplantation Society
  • Place of Presentation: Berlin，Germany
• [Presentation] Successful management of hepatic venous outflow obstruction in pediatric liver transplantation : A case report. (2012)
  • Author(s): Haga J
  • Organizer: International Pediatric Transplant Association
  • Place of Presentation: Nagoya，Japan
• [Presentation] Sustained Therapeutic Effects of Neo-islet Tissue Engineering by Islet Sheet Transplantation. (2012)
  • Author(s): Shimizu H
  • Organizer: The 24th International Congress of The Transplantation Society
  • Place of Presentation: Berlin，Germany
• [Presentation] 皮下膵島組織作成による糖尿病治療―300日の観察． (2012)
  • Author(s): 花山寛之
  • Organizer: 第11回日本再生医療学会
  • Place of Presentation: 横浜
• [Presentation] 膵島細胞シートの皮下移植における長期血糖制御能． (2012)
  • Author(s): 清水裕史
  • Organizer: 第11回日本組織移植学会総会・学術集会
  • Place of Presentation: 東京
• [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: 浦安
  • Year and Date: 2011-06-16
• [Presentation] 膵島移植の新たな展開-膵島細胞シートによる皮下での膵島組織作製- (2011)
  • Author(s): 清水裕史, 大橋一夫, 齊藤敬弘, 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)
  • Year and Date: 2011-06-16
• [Presentation] Functional islet tissue engineering in subcutaneoua site using fabricated islet cell sheets (2011)
  • Author(s): Shimizu H, Ohasi K, Saito T, Uto R, Ise K, Yamato M, Okano M, Gotoh M
  • Organizer: The 13^<th> 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, Sato N, Saito T, Ise K, Yamamoto M, Waguri S, Gotoh M
  • Organizer: The 13^<th> 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 fabricatedislet cell sheets (2011)
  • Author(s): Shimizu H, Ohasi K, Saito Takahiro, Uto R, Ise K, Yamato M, Okano M, Gotoh M
  • Organizer: The 13^<th> World Congress of International pancreas and islettransplantation 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 Takaharu, Anazawa T, Tsuchiya T, Kenjo A, Sato S, Sato N, Saito Takuro, Ise K, Yamamoto M, Waguri S, Go-toh M
  • Organizer: The 13^<th> World Congress of International pancreas and islettransplantation association
  • Place of Presentation: Prague.Czech Republic
  • Year and Date: 2011-06-03
• [Presentation] 膵島細胞移植の開発-膵島細胞シートによる皮下での膵島組織作製- (2011)
  • Author(s): 伊勢一哉, 大橋一夫, 齋藤敬弘, 清水裕史, 鵜頭理恵, 岡野光男, 後藤満一
  • Organizer: 第38回日本膵・膵島移植研究会
  • Place of Presentation: 奈良
  • Year and Date: 2011-03-05
• [Presentation] 膵島細胞移植の開発-膵島細胞シートによる皮下での膵島組織作製- (2011)
  • Author(s): 伊勢一哉, 大橋一夫, 齊藤敬弘, 清水裕史, 鵜頭理恵, 岡野光夫, 後藤満一
  • Organizer: 第38回日本膵・膵島移植研究会
  • Place of Presentation: 奈良県新公会堂(奈良県)
  • Year and Date: 2011-03-04
• [Presentation] 膵島移植の新たな手法-膵島細胞シートによる皮下の膵島組織作製- (2011)
  • Author(s): 齋藤敬弘, 大橋一夫, 清水裕史, 鵜頭理恵, 伊勢一哉, 岡野光男, 後藤満一
  • Organizer: 第10回日本再生医療学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-02
• [Presentation] 膵島移植の新たな手法-膵島細胞シートによる皮下での膵島組織作製- (2011)
  • Author(s): 齊藤敬弘, 大橋一夫, 清水裕史, 鵜頭理恵, 伊勢一哉, 岡野光夫, 後藤満一
  • Organizer: 第10回日本再生医療学会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 2011-03-02
• [Presentation] Cell Sheet Engineering Toward Bioengineering of Functional Neo-islets. (2010)
  • Author(s): Saito Takahiro
  • Organizer: The 23th International Congress of The Transplantation Society
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2010-08-16
• [Presentation] Mitomycin-C treatment significantly reduces central necrotic damage of islets in culture. (2010)
  • Author(s): Sai t o T, Sai t o T, Sa t o Y, Ise K, Oshibe I, Waguri S, Gotoh M
  • Organizer: The 23th International Congress of The Transplantation Society
  • Place of Presentation: Vancouver, Canada
• [Presentation] Cell Sheet Engineering Toward Bioengineering of Functional Neo-islets (2010)
  • Author(s): Saito T, Oohasi K, Uto R, Yamato M,Okano M, Simizu H, Ise K, Gotoh M
  • Organizer: The 23th International Congress of The Transplantation Society
  • Place of Presentation: Vancouver, Canada
• [Book] 膵島組織作製による糖尿病治療への展開 (2012)
  • Author(s): 伊勢一哉,大橋一夫,後藤満一
  • Publisher: 朝倉
• [Book] 代謝系臓器 (2012)
  • Author(s): 伊勢一哉
  • Total Pages: 212
  • Publisher: 朝倉書店