Production of the safer induced pluripotent stem cells and their application for regenerative medicine

• Project/Area Number: 20200076
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy; General medical chemistry
• Research Institution: National Institute of Biomedical Innovation
• Principal Investigator: 川端 健二 National Institute of Biomedical Innovation (50356234)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥31,070,000 (Direct Cost: ¥23,900,000、Indirect Cost: ¥7,170,000); Fiscal Year 2010: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000); Fiscal Year 2009: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000); Fiscal Year 2008: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
• Keywords: 発生生物学 / 再生医学

Research Abstract

Induced pluripotent stem (iPS) cells were produced by threetransduction systems, retroviral vectors, lentiviral vectors, and adenoviral vectors. The highest production efficiency was obtained when lentiviral vectors were used. This is because lentiviral vectors could show the highest transduction efficiency. When HoxB4 gene, PPARγ gene, and Runx2 gene were transduced with adenoviral vectors with the CA promoter, hematopoietic progenitor cells, adipocytes, and osteoblasts were efficiently induced, respectively, in comparison with conventional differentiation methods. These results demonstrate that adenoviral vectors could be a useful tool for efficient differentiation from iPS cells.

Research Products

• [Journal Article] Efficient generation of hepatoblasts from human ES cells and iPS cells by transient overexpression of homeobox gene HEX. (2011)
  • Author(s): Inamura M., Kawabata K., Takayama K., Tashiro K., Sakurai F., Katayama K., Toyoda M., Akutsu H., Miyagawa Y., Okita H., Kiyokawa N., Umezawa A., Hayakawa T., Furue MK., Mizuguchi H.
  • Journal Title: Mol. Ther. 19 Pages: 400-407
• [Journal Article] Efficient generation of hepatoblasts from human ES cells and iPS cells by transient overexpression of homeobox gene HEX. (2011)
  • Author(s): Inamura M, Kawabata K, Takayama K, Tashiro K, Sakurai F, Katayama K, Toyoda M, Akutsu H, Miyagawa Y, Okita H, Kiyokawa N, Umezawa A, Hayakawa T, Furue MK, Mizuguchi H.
  • Journal Title: Molecular Therapy Volume: 19 Pages: 400-407
  • Peer Reviewed
• [Journal Article] Induction of type I interferon by adenovirus-encoded small RNAs. (2010)
  • Author(s): Yamaguchi T., Kawabata K., Kouyama E., Ishii K.J., Katayama K., Suzuki T., Kurachi S., Sakurai F., Akira S., Mizuguchi H.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 107 Pages: 17286-17291
• [Journal Article] Differentiation of functional cells from iPS cells by efficient gene transfer. (2010)
  • Author(s): Kawabata K., Tashiro K., Mizuguchi H.
  • Journal Title: Yakugaku Zasshi. 130 Pages: 1527-1534
  • NAID: 130000451705
• [Journal Article] Adenovirus vector-mediated efficient transduction into human embryonic and induced pluripotent stem cells. (2010)
  • Author(s): Tashiro K., Kawabata K., Inamura M., Takayama K., Furukawa N., Sakurai F., Katayama K., Hayakawa T., Furue MK., Mizuguchi H.
  • Journal Title: Cell Reprogram. 12 Pages: 501-507
• [Journal Article] Adenovirus vector-mediated efficient transduction into human embryonic and induced pluripotent stem cells. (2010)
  • Author(s): Tashiro K, Kawabata K, Inamura M, Takayama K, Furukawa N, Sakurai F, Katayama K, Hayakawa T, Furue MK, Mizuguchi H.
  • Journal Title: Cell Reprogram. Volume: 12 Pages: 501-507
  • Peer Reviewed
• [Journal Article] Efficient adipocyte and osteoblast differentiation from mouse induced pluripotent stem cells by adenoviral transduction. (2009)
  • Author(s): Tashiro K., Inamura M., Kawabata K., Sakurai F., Yamanishi K., Hayakawa T., Mizuguchi H.
  • Journal Title: Stem Cells. 27 Pages: 102-1811
• [Journal Article] Efficient osteoblast differentiation from mouse bone marrow stromal cells with polylysin-modified adenovirus vectors. (2009)
  • Author(s): Tashiro K., Kondo A., Kawabata K., Sakurai H., Sakurai F., Yamanishi K., Hayakawa T., Mizuguchi H.
  • Journal Title: Biochem. Biophys. Res. Commun. 379 Pages: 127-132
• [Journal Article] Efficient adipocyte and osteoblast differentiation from mouse induced pluripotent stem cells by adenoviral transduction. (2009)
  • Author(s): Tashiro K, Inamura M, Kawabata K, Sakurai F, Yamanishi K, Hayakawa T, Mizuguchi H.
  • Journal Title: Stem Cells 27 Pages: 1802-1811
  • Peer Reviewed
• [Journal Article] Development of fiber-substituted adenovirus vectors containing foreign peptides in the adenovirus serotype 35 fiber knob. (2009)
  • Author(s): Matsui H, Sakurai F, Kurachi S, Tashiro K, Sugio K, Kawabata K, Yamanishi K, Mizuguchi H.
  • Journal Title: Gene Ther. 16 Pages: 1050-1057
  • Peer Reviewed
• [Journal Article] Efficient osteoblast differentiation from mouse bone marrow stromal cells with polylysin-modified adenovirus vectors (2009)
  • Author(s): Tashiro K, Kondo A, Kawabata K, Sakurai H, Sakurai F, Yamanishi K, Hayakawa T, Mizuguchi H.
  • Journal Title: Biochem. Biophys. Res. Commun. 379 Pages: 127-132
  • Peer Reviewed
• [Journal Article] Adenoviral expression of suppressor of cytokine signaling-1 reduces adenovirus vector-induced innate immune responses. (2008)
  • Author(s): Sakurai H., Tashiro K., Kawabata K., Yamaguchi T., Sakurai F., Nakagawa S., Mizuguchi H.
  • Journal Title: J.Immunol. 180 Pages: 4931-4938
• [Journal Article] Efficient adenovirus vector-mediated PPAR gamma gene transfer into mouse embryoid bodies promotes adipocyte differentiation. (2008)
  • Author(s): Tashiro K., Kawabata K., Sakurai H., Kurachi S., Sakurai F., Yamanishi K., Mizuguchi H.
  • Journal Title: J.Gene Med. 10 Pages: 498-507
• [Journal Article] Efficient adenovirus vector-mediated PPAR gamma gene transfer into mouse etnbryoid bodies promotes adipocyte differentiation (2008)
  • Author(s): Tashiro K, Kawabata K, Sakurai H, Kurachi S, Sakurai F, Yamanishi K,Mizuguchi H.
  • Journal Title: J. Gene Med. 10 Pages: 498-507
  • Peer Reviewed
• [Presentation] 遺伝子導入を用いたiPS細胞の肝細胞への高効率分化誘導法 (2011)
  • Author(s): 川端健二
  • Organizer: 第10回日本再生医療学会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2011-03-01
• [Presentation] 遺伝子導入を用いたiPS細胞の肝細胞への高効率分化誘導法 (2011)
  • Author(s): 川端健二、水口裕之
  • Organizer: 第10回日本再生医療学会総会
• [Presentation] 生体内VEGF過剰発現による造血幹細胞の動員効果 (2011)
  • Author(s): 野中昭希、田代克久、山口朋子、西川恵三、水口裕之、川端健二
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] HoxB4遺伝子の一過性発現によるマウスES/iPS細胞から血液細胞への分化誘導 (2011)
  • Author(s): 田代克久、大森美幸、櫻井文教、山口朋子、西川恵三、川端健二、水口裕之
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] iPS細胞からマスト細胞への分化誘導法の確立 (2011)
  • Author(s): 山口朋子、番匠谷研吾、田代克久、大森美幸、田中智之、西川恵三、水口裕之、川端健二
  • Organizer: 第10回日本再生医療学会総会
  • Place of Presentation: 東京
• [Presentation] 遺伝子導入を用いたiPS細胞の高効率分化誘導法 (2010)
  • Author(s): 川端健二
  • Organizer: 遺伝子デリバリー研究会第10回夏期セミナー
  • Place of Presentation: 大津
  • Year and Date: 2010-09-02
• [Presentation] 遺伝子導入を用いたiPS細胞の高効率分化誘導法 (2010)
  • Author(s): 川端健二
  • Organizer: 遺伝子デリバリー研究会第10回夏期セミナー
  • Place of Presentation: 滋賀(招待講演)
  • Year and Date: 2010-09-02
• [Presentation] Induction of hematopoietic differentiation from mouse embryonic and induced pluripotent stem cells by transient HoxB4 transduction. (2010)
  • Author(s): Katsuhisa Tashiro, Miyuki Omori, Tomoko Yamaguchi, Keizo Nishikawa, Fuminori Sakurai, Kenji Kawabata, Hiroyuki Mizuguchi.
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸
• [Presentation] アデノウイルスベクターによる遺伝子導入法を用いたマウスiPS細胞から造血幹細胞・血液前駆細胞への分化誘導 (2010)
  • Author(s): 大森美幸、田代克久、形山和史、櫻井文教、高木智、川端健二、水口裕之
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸
• [Presentation] iPS細胞への遺伝子導入を用いた分化誘導の最適化 (2010)
  • Author(s): 川端健二、田代克久、水口裕之
  • Organizer: 日本薬学会第130年会シンポジウム(招待講演)
  • Place of Presentation: 岡山
• [Presentation] アデノウイルスベクターを用いたiPS細胞への遺伝子導入の最適化と分化誘導(招待講演) (2009)
  • Author(s): 川端健二
  • Organizer: 日本生化学会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] Adenovirus vector-mediated differentiation into adipocytic and osteoblastic lineages from mouse induced pluripotent stem (iPS) cells (2009)
  • Author(s): Kawabata K
  • Organizer: American Society of Gene Therapy
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2009-05-08
• [Presentation] アデノウイルスベクターを用いたiPS細胞への遺伝子導入の最適化と分化誘導 (2009)
  • Author(s): 川端健二、田代克久、水口裕之
  • Organizer: 第82回日本生化学会大会シンポジウム(招待講演)
  • Place of Presentation: 神戸
• [Presentation] Reduction of vector-induced innate immunity by SOCS1-expressing adenovirus vector (2008)
  • Author(s): 川端健二
  • Organizer: 日本遺伝子治療学会
  • Place of Presentation: 札幌
  • Year and Date: 2008-06-12
• [Presentation] SOCS1-expressing adenovirus vectors can suppress vector-induced innate immunity (2008)
  • Author(s): Kawabata K
  • Organizer: American Society of Gene Therapy
  • Place of Presentation: Boston(USA)
  • Year and Date: 2008-05-31
• [Book] Efficient hepatic differentiation from human iPS cells by gene transfer. Liver Stem Cells : Methods and Protocols.
  • Author(s): Kawabata K., Inamura M., Mizuguchi H.
  • Publisher: Humana Press. USA (part of the Springer publishing group).(in press.)
• [Remarks] ホームページ等
  • URL: http://www.nibio.go.jp/Proj3HP/index.html
• [Remarks]
  • URL: http://www.nibio.go.jp/Proj3HP/index.html
• [Remarks]
  • URL: http://www.nibio.go.jp/Proj3HP/index.html
• [Remarks]
  • URL: http://www.nibio.go.jp/Proj3HP/index.html
• [Patent(Industrial Property Rights)] 幹細胞から肝細胞への分化誘導方法 (2010)
  • Inventor(s): 水口裕之、川端健二、古江美保、稲村充
  • Industrial Property Rights Holder: ヒューマンサイエンス振興財団
  • Industrial Property Number: 2010-121282
  • Acquisition Date: 2010-05-27
• [Patent(Industrial Property Rights)] 幹細胞から肝細胞への分化誘導方法 (2010)
  • Inventor(s): 水口裕之、川端健二、稲村充、古江美保
  • Industrial Property Rights Holder: 財団法人ヒューマンサイエンス振興財団
  • Industrial Property Number: 2010-121282
  • Filing Date: 2010-05-27
• [Patent(Industrial Property Rights)] 幹細胞から肝細胞への分化誘導方法 (2009)
  • Inventor(s): 水口裕之、川端健二、稲村充、古江美保
  • Industrial Property Rights Holder: 財団法人ヒューマンサイエンス振興財団
  • Industrial Property Number: 2009-247342
  • Filing Date: 2009-10-28