Development of angiogeneic pancreatic islets using iPS cell-derived pancreatic islet cells

• Project/Area Number: 17K19692
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Fukuoka University
• Principal Investigator: SAKATA Naoaki 福岡大学, 医学部, 准教授 (50431565)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 膵島移植 / 血管化 / 移植・再生医療

Outline of Final Research Achievements

Islet transplantation is a cellular therapy for improving control of blood glucose by transplantation of islets. The major obstacles of the therapy are limited donor supplies and ischemia. In this study, we attempted to develop angiogeneic islets using rodents and using human iPS cell-derived islet cells. We succeeded to develop angiogeneic islets using islets acquired from mice and certified decrease of blood glucose after transplantation of the angiogeneic islets.

Academic Significance and Societal Importance of the Research Achievements

本研究は、移植する膵島にあらかじめ血管を付帯させる、いわゆる血管化膵島を開発する研究であり、特にiPS細胞由来の膵島細胞を用いた血管化膵島の開発を目指した。結果、マウス膵島からなる血管化膵島の作成と移植実験における有効性という点で一定の成果を挙げることができた。今後、iPS細胞はもちろんのこと、ブタなどの大型動物を利用した血管化膵島を実用化することができれば、膵島移植におけるドナー不足の問題が解決し、多くの重症糖尿病患者がこの治療の恩恵を受けられるようになると期待される。

Research Products

• [Journal Article] Regenerative and Transplantation Medicine: Cellular Therapy Using Adipose Tissue-Derived Mesenchymal Stromal Cells for Type 1 Diabetes Mellitus (2019)
  • Author(s): Takahashi Hiroyuki、Sakata Naoaki、Yoshimatsu Gumpei、Hasegawa Suguru、Kodama Shohta
  • Journal Title: Journal of Clinical Medicine Volume: 8 Issue: 2 Pages: 249-249
  • DOI: 10.3390/jcm8020249
  • Peer Reviewed / Open Access
• [Journal Article] Combination of longitudinal pancreaticojejunostomy with coring-out of the pancreatic head (Frey procedure) and distal pancreatectomy for chronic pancreatitis (2019)
  • Author(s): Sato Hideaki、Ishida Masaharu、Motoi Fuyuhiko、Sakata Naoaki、Aoki Takeshi、Suzuki Hideyuki、Yamamura Akihiro、Karasawa Hideaki、Hata Tatsuo、Ohtsuka Hideo、Mizuma Masamichi、Morikawa Takanori、Hayashi Hiroki、Nakagawa Kei、Kamei Takashi、Naitoh Takeshi、Egawa Shinichi、Unno Michiaki
  • Journal Title: Surgery Today Volume: 49 Issue: 2 Pages: 137-142
  • DOI: 10.1007/s00595-018-1720-1
  • Peer Reviewed
• [Journal Article] FBXW7 modulates malignant potential and cisplatin-induced apoptosis in cholangiocarcinoma through NOTCH1 and MCL1 (2018)
  • Author(s): Mori Akiko、Masuda Kunihiro、Ohtsuka Hideo、Shijo Masahiro、Ariake Kyohei、Fukase Koji、Sakata Naoaki、Mizuma Masamichi、Morikawa Takanori、Hayashi Hiroki、Nakagawa Kei、Motoi Fuyuhiko、Naitoh Takeshi、Fujishima Fumiyoshi、Unno Michiaki
  • Journal Title: Cancer Science Volume: 109 Issue: 12 Pages: 3883-3895
  • DOI: 10.1111/cas.13829
  • Peer Reviewed / Open Access
• [Journal Article] Lymph nodes around the posterior gastric artery: their existence, frequency, and clinical implications (2018)
  • Author(s): Ishii Kentaro、Ishida Masaharu、Sugisawa Norihiko、Murakami Megumi、Ono Tomoyuki、Tachibana Tomoyoshi、Imoto Hirofumi、Aoki Takeshi、Kudoh Katsuyoshi、Ohnuma Shinobu、Sakata Naoaki、Musha Hiroaki、Morikawa Takanori、Motoi Fuyuhiko、Kamei Takashi、Naitoh Takeshi、Unno Michiaki
  • Journal Title: Surgery Today Volume: 48 Issue: 10 Pages: 916-920
  • DOI: 10.1007/s00595-018-1677-0
  • Peer Reviewed
• [Journal Article] A novel liver metastasis-correlated protein of pancreatic neuroendocrine neoplasm (PanNEN) discovered by proteomic analysis (2018)
  • Author(s): Shimura Mitsuhiro、Mizuma Masamichi、Takadate Tatsuyuki、Katoh Yasutake、Suzuki Takashi、Iseki Masahiro、Hata Tatsuo、Aoki Shuichi、Suzuki Yukie、Sakata Naoaki、Ohtsuka Hideo、Hayashi Hiroki、Morikawa Takanori、Nakagawa Kei、Motoi Fuyuhiko、Naitoh Takeshi、Igarashi Kazuhiko、Sasano Hironobu、Unno Michiaki
  • Journal Title: Oncotarget Volume: 9 Issue: 36 Pages: 24291-24303
  • DOI: 10.18632/oncotarget.25110
  • Peer Reviewed / Open Access
• [Journal Article] The Spleen as an Optimal Site for Islet Transplantation and a Source of Mesenchymal Stem Cells. (2018)
  • Author(s): Sakata, N., Yoshimatsu, G., and Kodama, S.
  • Journal Title: Int J Mol Sci Volume: 19 Issue: 5 Pages: 1391-1391
  • DOI: 10.3390/ijms19051391
  • Peer Reviewed / Open Access
• [Journal Article] Frey's procedure for chronic pancreatitis improves the nutritional status of these patients. (2018)
  • Author(s): Sato H, Ishida M, Motoi F, Sakata N, Aoki T, Kudoh K, Ohtsuka H, Mizuma M, Morikawa T, Hayashi H, Nakagawa K, Naitoh T, Egawa S, Unno M.
  • Journal Title: Surg Today Volume: 48 Issue: 1 Pages: 80-86
  • DOI: 10.1007/s00595-017-1557-z
  • Peer Reviewed
• [Journal Article] A long-term survival case treated with conversion surgery following chemotherapy after diagnostic metastasectomy for pancreatic cancer with synchronous liver metastasis (2017)
  • Author(s): Shimura M, Mizuma M, Hayashi H, Mori A, Tachibana T, Hata T, Iseki M, Takadate T, Ariake K, Maeda S, Ohtsuka H, Sakata N, Morikawa T, Nakagawa K, Naitoh T, Kamei T, Motoi F, Unno M.
  • Journal Title: Surg Case Rep Volume: 3 Issue: 1 Pages: 132-132
  • DOI: 10.1186/s40792-017-0409-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pleckstrin homology-like domain family A, member 3 (PHLDA3) deficiency improves islets engraftment through the suppression of hypoxic damage. (2017)
  • Author(s): Sakata N, Yamaguchi Y, Chen Y, Shimoda M, Yoshimatsu G, Unno M, Sumi S, Ohki R.
  • Journal Title: PLoS One Volume: 12 Issue: 11 Pages: e0187927-e0187927
  • DOI: 10.1371/journal.pone.0187927
  • NAID: 120006878515
  • Peer Reviewed / Open Access
• [Journal Article] The comparative anatomy of the folds, fossas, and adhesions around the duodenojejunal flexure in mammals. (2017)
  • Author(s): Ishida M, Sakata N, Ise I, Ono T, Shimura M, Ishii K, Murakami M, Takadate T, Aoki T, Kudo K, Ohnuma S, Fukase K, Ohtsuka H, Mizuma M, Hayashi H, Nakagawa K, Morikawa T, Motoi F, Naitoh T, Unno M.
  • Journal Title: Folia Morphol Volume: - Issue: 2 Pages: 286-292
  • DOI: 10.5603/fm.a2017.0089
  • Peer Reviewed / Open Access
• [Journal Article] Application of Quantitative Targeted Absolute Proteomics to Profile Protein Expression Changes of Hepatic Transporters and Metabolizing Enzymes During Cholic Acid-Promoted Liver Regeneration. (2017)
  • Author(s): Miura T, Tachikawa M, Ohtsuka H, Fukase K, Nakayama S, Sakata N, Motoi F, Naitoh T, Katayose Y, Uchida Y, Ohtsuki S, Terasaki T, Unno M.
  • Journal Title: J Pharm Sci Volume: 106 Issue: 9 Pages: 2499-2508
  • DOI: 10.1016/j.xphs.2017.02.018
  • Peer Reviewed
• [Presentation] 当講座における膵島移植研究 (2019)
  • Author(s): 坂田直昭
  • Organizer: 福岡大学再生医学研究所 平成30年度研究報告会 第５回再生医学研究セミナー
• [Presentation] 移植膵島を同定するための画像検査について (2019)
  • Author(s): 坂田直昭
  • Organizer: 第18回日本再生医療学会総会
• [Presentation] IP-10をターゲットとした門脈内膵島移植における自然免疫反応の制御 (2019)
  • Author(s): 吉松軍平
  • Organizer: 第46回日本膵・膵島移植研究会
• [Presentation] 精巣上体周囲脂肪組織被覆膵島移植より腹腔内膵島移植の概念を考える (2019)
  • Author(s): 坂田直昭
  • Organizer: 第46回日本膵・膵島移植研究会
• [Presentation] 慢性膵炎に対する膵全摘術＋自家膵島移植に関する提言 (2019)
  • Author(s): 坂田直昭
  • Organizer: 第46回日本膵・膵島移植研究会
• [Presentation] The impact of islet purity on metabolic outcome after islet transplantation into portal vein. (2019)
  • Author(s): Gumpei Yoshimatsu
  • Organizer: The 1st Congress of APITA (Asian Pancreas and Islet Transplant Association)
  • Int'l Joint Research
• [Presentation] Cooperation among the donor coordinators, islet transplant facilities, and transplant associations for pancreas or islet is necessary to promote the islet transplantation. (2019)
  • Author(s): Ayana Esaki
  • Organizer: The 1st Congress of APITA (Asian Pancreas and Islet Transplant Association)
  • Int'l Joint Research
• [Presentation] Intraperitoneal Islet Transplantation by Rolling-up Method Using Epididymal Adipose Tissue. (2019)
  • Author(s): Naoaki Sakata
  • Organizer: The 1st Congress of APITA (Asian Pancreas and Islet Transplant Association)
  • Int'l Joint Research
• [Presentation] 膵島移植とその現状 (2018)
  • Author(s): 坂田直昭
  • Organizer: Fukuoka Diabetes Academy 2018
  • Invited
• [Presentation] 異種膵島移植の今後の展望について (2018)
  • Author(s): 小玉正太
  • Organizer: 第54回日本移植学会総会
  • Invited
• [Presentation] 膵切後脂肪肝の基礎的・臨床的検討 (2018)
  • Author(s): 石田晶玄
  • Organizer: 第104回日本消化器病学会総会
• [Presentation] 腹腔動脈接触角度と術前治療有無からみた，当科DP-CAR症例の予後の検討 (2018)
  • Author(s): 林 洋毅
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] 新分類（type1，type2）による胆管内乳頭状腫瘍（IPNB）切除例の検討 (2018)
  • Author(s): 水間正道
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] Lateral pancreatico-jejunostomy (2018)
  • Author(s): 石田晶玄
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] 切除不能膵癌に対するConversion Surgery（CS）の適応：無再発生存期間の目標設定に基づくCS実施基準の再考 (2018)
  • Author(s): 元井冬彦
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] 膵神経内分泌腫瘍のWHO2017分類におけるNET-G3とNEC-G3の比較検討 (2018)
  • Author(s): 青木 豪
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] 重症急性胆嚢炎の治療戦略 (2018)
  • Author(s): 大塚 英郎
  • Organizer: 第118回日本外科学会定期学術集会
• [Remarks] 福岡大学研究者情報
  • URL: http://resweb2.jhk.adm.fukuoka-u.ac.jp/FukuokaUnivHtml/info/7263/R108J.html
• [Remarks] researchmap
  • URL: http://resweb2.jhk.adm.fukuoka-u.ac.jp/FukuokaUnivHtml/info/7263/R108J.html