Differentiation of human iPS cells into hepatocytes by using hepatic stellate cells

• Project/Area Number: 22659039
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Osaka City University
• Principal Investigator: IKEDA Kazuo 大阪市立大学, 大学院・医学研究科, 教授 (80275247)
• Co-Investigator(Renkei-kenkyūsha): CHEN Hui 名古屋市立大学, 大学院・医学研究科, 研究員 (70569003)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,030,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: iPS細胞 / 肝星細胞 / 肝細胞 / 肝芽細胞 / HEX / センダイウイルス

Research Abstract

Induced pluripotent stem(iPS) cells have remarkable potential of differentiating into various cell lineages, including hepatocytes. Hepatocytes induced from iPS cells are expected to have medical applications such as biomedical research, drug study and regenerative medicine. In this study, we tried to induce hepatocyte-like cells from human iPS cells by using hepatic stellate cells as feeder cells, and analyze expression level of Oct3/4, GATA4, alpha-fetoprotein and albumin to compare their properties of differentiation into hepatocytes.

Research Products

• [Journal Article] MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis (2012)
  • Author(s): Ogawa T, Enomoto M, Fujii H, Sekiya Y, Yoshizato K, Ikeda K, Kawada N.
  • Journal Title: Gut.
• [Journal Article] Suppression of hepatic stellate cell activation by microRNA-29b (2011)
  • Author(s): Sekiya Y, Ogawa T, Yoshizato K, Ikeda K, Kawada N.
  • Journal Title: Biochem Biophys Res Commun Volume: 412(1) Pages: 74-9
• [Journal Article] Down-regulation of cyclin E1 expression by microRNA-195 accounts for interferon-beta-induced inhibition of hepatic stellate cell proliferation (2011)
  • Author(s): Sekiya Y, Ogawa T, Iizuka M, Yoshizato K, Ikeda K, Kawada N.
  • Journal Title: J Cell Physiol Volume: 226(10) Pages: 2535-42
• [Journal Article] Promotion of liver and lung tumorigenesis in DEN-treated cytoglobin-deficient mice (2011)
  • Author(s): Thuy le TT, Morita T, Yoshida K, Wakasa K, Iizuka M, Ogawa T, Mori M, Sekiya Y, Momen S, Motoyama H, Ikeda K, Yoshizato K, Kawada N.
  • Journal Title: Am J Pathol Volume: 179(2) Pages: 1050-60
• [Journal Article] Pitavastatin inhibits hepatic steatosis and fibrosis in non-alcoholic steatohepatitis model rats (2011)
  • Author(s): Miyaki T, Nojiri S, Shinkai N, Kusakabe A, Matsuura K, Iio E, Takahashi S, Yan G, Ikeda K, Joh T.
  • Journal Title: Hepatol Res Volume: 41(4) Pages: 375-85
  • NAID: 10031144102
• [Journal Article] Promotion of liver and lung tumorigenesis in DEN-treated cytoglobin-deficient mice (2011)
  • Author(s): Thuy le TT, Morita T, Ikeda K, et al
  • Journal Title: Am J Pathol Volume: 179(2) Pages: 1050-1060
  • Peer Reviewed
• [Journal Article] Laminin-511, inducer of hairgrowth, is down-regulated and its suppressor in hair growth, laminin-332 up-regulated in chemotherapy-induced alopecia (2010)
  • Author(s): Imanishi H, Tsuruta D, Tateishi C, Sugawara K, Paus R, Tsuji T, Ishii M, Ikeda K, Kunimoto H, Nakajima K, Jones JC, Kobayashi H.
  • Journal Title: J Dermatol Sci Volume: 58(1) Pages: 43-54
  • NAID: 10027400358
• [Journal Article] Dynamic relationship of focal contacts and hemidesmosome protein complexes in live cells (2010)
  • Author(s): Ozawa T, Tsuruta D, Jones JC, Ishii M, Ikeda K, Harada T, Aoyama Y, Kawada A, Kobayashi H.
  • Journal Title: J Invest Dermatol Volume: 130(6) Pages: 1624-35
• [Journal Article] Dynamic relationship of focal contacts and hemidesmosome protein complexes in live cells (2010)
  • Author(s): Ozawa T, Tsuruta D, Ikeda K, et al
  • Journal Title: J Invest Dermatol Volume: 130(6) Pages: 1624-1635
  • Peer Reviewed
• [Journal Article] Laminin-511, inducer of hair growth, is down-regulated and its suppress or in hair growth, laminin-332 up-regulated in chemotherapy-induced alopecia (2010)
  • Author(s): Imanishi H, Tsuruta D, Ikeda K, et al
  • Journal Title: J Dermatol Sci Volume: 58(1) Pages: 43-54
  • NAID: 10027400358
  • Peer Reviewed
• [Journal Article] Suppression of type I collagen production by microRNA-29b in cultured human stellate cells (2010)
  • Author(s): Ogawa T, Iizuka M, Ikeda K, et al
  • Journal Title: Biochem Biophys Res Commun Volume: 391(1) Pages: 316-321
  • Peer Reviewed
• [Presentation] 慢性肝疾患における肝線維化マーカーとしてのマイクロRNAの有用性 (2011)
  • Author(s): 飯塚昌司, 小川智弘, 榎本大, 関谷由美子, 吉里勝利, 池田一雄, 河田則文
  • Organizer: 第25回肝類洞壁細胞研究会
  • Place of Presentation: 東京ガーデンパレス
  • Year and Date: 2011-12-17
• [Presentation] ヒトiPS細胞の肝細胞への分化誘導とiPS細胞由来肝細胞のマウス胎児肝臓への移植方法の検討 (2011)
  • Author(s): 杉山良典, 立野知世, 河田則文, 池田一雄
  • Organizer: 第39回日本肝臓学会西部会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2011-12-09
• [Presentation] Induction of the activation of stellate cells and the progression of liver fibrosis by microRNA-222 Hepatology (2011)
  • Author(s): Enomoto M, Ogawa T, Iizuka M, Fujii H, Tamori A, Yoshizato K, Ikeda K, Kawda N.
  • Year and Date: 2011-11-06
• [Presentation] マウス胎児肝臓へのヒトiPS細胞由来肝細胞の移植方法の検討 (2011)
  • Author(s): 杉山良典, 立野知世, 吉里勝利, 池田一雄
  • Organizer: 第18回肝細胞研究会
  • Place of Presentation: 東京ガーデンパレス
  • Year and Date: 2011-06-24
• [Presentation] マウス胎仔肝臓へのヒトiPS細胞由来肝細胞の移植方法の検討 (2011)
  • Author(s): 杉山良典、池田一雄
  • Organizer: 第18回肝細胞研究会
  • Place of Presentation: 東京ガーデンパレス
  • Year and Date: 2011-06-24
• [Presentation] miR-195の肝星細胞増殖における役割についての検討 (2011)
  • Author(s): 関谷由美子, 小川智弘, 飯塚昌司, 吉里勝利, 池田一雄, 河田則文
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: ホテルグランパシフィック
  • Year and Date: 2011-06-03
• [Presentation] 塩尻信義マウス肝臓発生過程におけるsyntaxin2の発現と肝芽細胞の増殖・分化に対する影響 (2010)
  • Author(s): 杉山良典、富谷智明、池田一雄、小池亨
  • Organizer: 第17回肝細胞研究会
  • Place of Presentation: 秋田アトリオン
  • Year and Date: 2010-06-19
• [Presentation] I型インターフェロンのマイクロRNA発現調節を介した肝星細胞増殖抑制作用 (2010)
  • Author(s): 関谷由美子, 小川智弘, 飯塚昌司, 吉里勝利, 池田一雄, 河田則文
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
  • Year and Date: 2010-05-27
• [Presentation] マイクロRN Aによる肝星細胞のI型コラーゲン発現制御 (2010)
  • Author(s): 飯塚昌司, 小川智弘, 関谷由美子, 吉里勝利, 池田一雄, 河田則文
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
  • Year and Date: 2010-05-27
• [Remarks]
  • URL: http://www.med.osaka-cu.ac.jp/anatomy1/