Development and verification of implantable pancreatic epithelial cells from human pluripotent stem cell

• Project/Area Number: 25860747
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Kyoto University
• Principal Investigator: TOYODA Taro 京都大学, iPS細胞研究所, 特定拠点助教 (60593530)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: iPS細胞 / ES細胞 / PDX1 / NKX6.1 / 膵臓 / 糖尿病 / β細胞 / インスリン

Outline of Final Research Achievements

Pancreatic bud/epithelial cells (NKX6.1+ cells) are considered as pancreas committed cells. Induction of the NKX6.1+ cell is a critical step for the generation of pancreatic cells from human pluripotent stem cells. However the induction protocol is not established. In this study we demonstrated that cellular aggregation is a key factor for induction of NKX6.1+ cells. Our generated NKX6.1+ cells expressed marker genes for pancreatic bud cells and could differentiate into pancreatic epithelia-like structures and beta cellｓ which secrete insulin in response to glucose level after implantation. Our new protocol is useful for basic research and clinical application using pancreatic cells.

Research Products

• [Journal Article] Cell aggregation optimizes the differentiation of human ESCs and iPSCs into pancreatic bud-like progenitor cells (2015)
  • Author(s): Toyoda T, Mae S, Tanaka H, Kondo Y, Funato M, Hosokawa Y, Sudo T, Kawaguchi Y, Osafune K
  • Journal Title: Stem Cell Resarch Volume: 14 Issue: 2 Pages: 185-197
  • DOI: 10.1016/j.scr.2015.01.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 多能性幹細胞を用いた腎臓、膵臓系譜の分化誘導研究の最前線 (2015)
  • Author(s): 居神麻衣子、豊田太郎、長船健二
  • Journal Title: 実験医学 Volume: 33 Pages: 260-266
• [Journal Article] 膵β細胞の再生医療―どこまで進んだのか― (2014)
  • Author(s): 木村東、豊田太郎、長船健二
  • Journal Title: プラクティス Volume: 31 Pages: 475-482
• [Journal Article] A novel efficient feeder-free culture system for the derivation of human induced pluripotent stem cells. (2014)
  • Author(s): Nakagawa M, Taniguchi Y, Senda S, Takizawa N, Ichisaka T, Asano K, Morizane A, Doi D, Takahashi J, Nishizawa M, Yoshida Y, Toyoda T, Osafune K, Sekiguchi K, YamanakaS.
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 3594-3594
  • DOI: 10.1038/srep03594
  • NAID: 120005357344
  • Peer Reviewed
• [Presentation] 細胞塊形成を利用したヒトES/iPS細胞から移植可能な膵芽細胞への分化誘導 (2015)
  • Author(s): 豊田太郎、木村東、前伸一、田中ひろみ、長船健二
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2015-03-19 – 2015-03-21
• [Presentation] Cell aggregation optimizes the differentiation of human ESCs and iPSCs into pancreatic bud-like progenitor cells (2015)
  • Author(s): Taro Toyoda, Shin-Ichi Mae, Azuma Kimura, Hiromi Tanaka, Yasushi Kondo, Michinori Funato, Yoshiya Hosokawa, Tomomi Sudo, Yoshiya Kawaguchi, Kenji Osafune
  • Organizer: 第18回武田科学振興財団生命科学シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2015-01-15 – 2015-01-17
• [Presentation] A small molecule that facilitates the differentiation into pancreatic endocrine cells from human ES/iPS cells (2014)
  • Author(s): Yasushi Kondo, Taro Toyoda, Michinori Funato, Yoshiya Hosokawa, Satoshi Matsui, Tomomi Sudo, Xiaotong Zhuang, Akira Ohta, Shinya Yamanaka, Nobuya Inagaki, Kenji Osafune
  • Organizer: 10th International Diabetes Federation (IDF)-Western Pacific Region Congress 2014/ 6th Asian Association for the Study of Diabetes (AASD) Scientific Meeting
  • Place of Presentation: Singapore, Singapore
  • Year and Date: 2014-11-21 – 2014-11-24
• [Presentation] CELL AGGREGATION OPTIMIZES THE DIFFERENTIATION INTO PANCREATIC BUD-LIKE PROGENITOR CELLS FROM HUMAN ESCS AND IPSCS (2014)
  • Author(s): Taro Toyoda, Shin-Ichi Mae, Hiromi Tanaka, Yasushi Kondo, Michinori Funato, Yoshiya Hosokawa, Tomomi Sudo, Shinya Yamanaka, Kenji Osafune
  • Organizer: 12th Annual Meeting, International Society for Stem Cell Research
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2014-06-18 – 2014-06-21
• [Presentation] DEVELOPMENT OF A NOVEL XENO-FREE MEDIUM, STEMFITTM, FOR FEEDER-FREE CULTURE OF HUMAN INDUCED PLURIPOTENT STEM CELLS (2014)
  • Author(s): Senda S, Okamoto S, Taniguchi Y, Ozawa H, Ando Y, Yokoyama M, Matsumoto T, Kobayashi T, Takizawa N, Ichisaka T, Asano K, Morizane A, Doi D, Takahashi T, Yoshida Y, Toyoda T, Osafune K, Itoga J, Yagi E, Nishizawa M, Yamanaka S, Sekiguchi K, Nakagawa M
  • Organizer: 12th Annual Meeting, International Society for Stem Cell Research
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2014-06-18 – 2014-06-21
• [Presentation] Development of the Method to Differentiate Pancreatic ß-like Cells from Human iPS Cells by Using Small Molecules (2014)
  • Author(s): Yasushi Kondo, Kentaro Toyoda, Taro Toyoda, Michinori Funato, Yoshiya Hosokawa Satoshi Matsui, Tomomi Sudo, Xiaotong Zhuang, Akira Ohta, Shinya Yamanaka, Nobuya Inagaki, Kenji Osafune
  • Organizer: American Diabetes Association 74th Scientific Sessions
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-06-13 – 2014-06-17
• [Presentation] ヒトiPS/ES細胞からの移植可能な膵芽細胞への分化誘導法の開発 (2014)
  • Author(s): 豊田太郎、前伸一、田中ひろみ、近藤恭士、舩戸道徳、細川吉弥、須藤智美、山中伸弥、長船健二
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] 病態モデル作製に向けたヒトiPS/ES細胞から膵外分泌細胞への高効率分化誘導法の開発 (2014)
  • Author(s): 舩戸 道徳、豊田 太郎、近藤 恭士、細川 吉弥、須藤 智美、沖田 圭介、浅香勲、上杉 志成、加藤 善一郎、太田 章、山中 伸弥、近藤 直実、長船 健二
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] Development of an efficient differentiation method from iPSCs/ESCs into pancreatic exocrine lineages towards novel pancreatic disease models (2013)
  • Author(s): Funato M, Toyoda T, Kondo Y, Hosokawa Y, Sudo T, Okita K, Asaka I, Uesugi M, Kato ZI, Ohta A, Yamanaka S, Kondo N, Osafune K
  • Organizer: 11th Annual Meeting, International Society for Stem Cell Research
  • Place of Presentation: Boston Convention and Exhibition Center, Boston, MA, USA
• [Presentation] Development of the differentiation method from human iPSCs into pancreatic β cells using small molecules (2013)
  • Author(s): Kondo Y, Toyoda T, Funato M, Hosokawa Y, Sudo T, Zhuang X, Toyoda K, Ohta A, Yamanaka S, Inagaki N, Osafune K
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本キャッスルホテル（熊本）
• [Presentation] ケミカルバイオロジーを用いたヒトiPS細胞から膵β細胞への分化誘導研究 (2013)
  • Author(s): 近藤 恭士、豊田 太郎、稲垣 暢也、長船 健二
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本キャッスルホテル（熊本）
  • Invited
• [Book] 膵島の再生医療 (2015)
  • Author(s): 豊田太郎、長船健二
  • Total Pages: 173
  • Publisher: 診断と治療社
• [Book] 遺伝子医学 MOOK27 iPS細胞を用いた難病研究・臨床病態解明と創薬に向けた研究の最新知見 (2015)
  • Author(s): 細川 吉弥、豊田 太郎、長船 健二
  • Total Pages: 228
  • Publisher: メディカルドゥ
• [Book] 腎と透析 (iPS細胞を用いた糖尿病に対する再生医療) (2013)
  • Author(s): 細川 吉弥、豊田 太郎、長船 健二
  • Total Pages: 144
  • Publisher: 東京医学社
• [Remarks] 糖尿病治療に向けてヒトES/iPS細胞から移植用の膵細胞を効率よく作製する方法を開発
  • URL: https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/150205-084839.html
• [Patent(Industrial Property Rights)] 膵芽細胞の製造方法および膵芽細胞を含む膵疾患治療剤 (2014)
  • Inventor(s): 長船健二、豊田太郎
  • Industrial Property Rights Holder: 長船健二、豊田太郎
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-105049
  • Filing Date: 2014-05-21
• [Patent(Industrial Property Rights)] 膵ホルモン産生細胞の製造方法 (2013)
  • Inventor(s): 長船健二、稲垣暢也、豊田太郎、近藤恭士
  • Industrial Property Rights Holder: 長船健二、稲垣暢也、豊田太郎、近藤恭士
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-164137
  • Filing Date: 2013-08-07