Development of cell therapy using induced pluripotent stem cells for dogs with spinal cord injury

• Project/Area Number: 22658101
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Clinical veterinary science
• Research Institution: Osaka Prefecture University
• Principal Investigator: INABA Toshio 大阪府立大学, 生命環境科学研究科, 教授 (00137241)
• Co-Investigator(Kenkyū-buntansha): IMAI Hiroshi 京都大学, 農学研究科, 教授 (10303869) ; SHUGIURA Kikuya 大阪府立大学, 生命環境科学研究科, 准教授 (30171143) ; HATOYA Shingo 大阪府立大学, 生命環境科学研究科, 助教 (40453138)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,440,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥2,400,000 (Direct Cost: ¥2,400,000)
• Keywords: 獣医学 / トランスレーショナルリサーチ / バイオテクノロジー / 移植・再生医療 / 発生・分化 / iPS細胞 / イヌ / ES細胞 / 骨髄間質細胞 / 脊髄損傷 / 神経細胞 / 遺伝子導入 / 再生医療

Research Abstract

The objective of this study was to development of cell therapy using induced pluripotent stem(iPS) cells for dogs with spinal cord injury, and the following results were obtained.(1) We successfully reprogrammed canine embryonic fibroblasts into iPS-like cells using lentiviruses containing 4 transcription factors. Canine iPS-like cell colonies displayed a mouse embryonic stem(ES) cell-like morphology, differentiated to multiple cell types in vitro, and maintained their proliferation and mouse ES-like morphology beyond passage 25.(2) Neurons could be induced from canine iPS-like cells.(3) Bone marrow stromal cell transplantation caused no complications and could have beneficial effects on functional recovery of dogs with spinal cord injury, and further studies are required to apply iPS-like cells for the treatment of these dogs.

Research Products

• [Journal Article] Methods for cell harvesting and the biological properties of canine bone marrow stromal cells at successive passages (2012)
  • Author(s): Nishida H, Shoji Y, Nakamura M, Hatoya S, Sugiura K, Yamate J, Kuwamura M, Kotani T, Nakayama M, Suzuki Y, Ide C, Inaba T
  • Journal Title: Am. J. Vet. Res Volume: (印刷中) Issue: 8 Pages: 1118-1123
  • DOI: 10.2460/ajvr.72.8.1118
  • Peer Reviewed
• [Journal Article] Safety of autologous bone marrow stromal cell transplantation in dogs with acute spinal cord injury (2012)
  • Author(s): Nishida H, Nakayama M, Tanaka H, Kitamura M, Hatoya S, Sugiura K, Harada Y, Suzuki Y, Ide C, Inaba T
  • Journal Title: Vet. Surg Volume: (印刷中) Issue: 4 Pages: 437-442
  • DOI: 10.1111/j.1532-950x.2011.00959.x
  • Peer Reviewed
• [Journal Article] Methods for cell harvesting and the biological properties of canine bone marrow stromal cells at successive passages (2012)
  • Author(s): Hidetaka Nishida, et al
  • Journal Title: American Journal of Veterinary Research Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Simple and efficient method for generation of induced pluripotent stem cells using piggyBac transposition of doxycycline-inducible factors and an EOS reporter system (2011)
  • Author(s): Tsukiyama T., Asano R., Kawaguchi T., Kim N., Yamada M., Minami N., Ohinata Y. and Imai H
  • Journal Title: Genes to Cells Volume: 16 Issue: 7 Pages: 815-825
  • DOI: 10.1111/j.1365-2443.2011.01528.x
  • NAID: 120005593680
  • Peer Reviewed
• [Journal Article] Induction of fertile oestrus in dioestrous bitches by prostaglandin F2α and a GnRH-agonist (2011)
  • Author(s): Ohmura M, Torii R, Hatoya S, Sugiura K, Tamada H, Kawate N, Takahashi M, Sawada T, Inaba T
  • Journal Title: Vet. Rec Volume: 168巻 Issue: 25 Pages: 669-669
  • DOI: 10.1136/vr.d1183
  • Peer Reviewed
• [Journal Article] Locomotor improvement after autologous bone marrow stromal cell intrathecal delivery in dogs with chronic spinal cord injury (2011)
  • Author(s): Hidetaka Nishida, et al
  • Journal Title: American Journal of Veterinary Research Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Induction of fertile oestrus in dioestrous bitches by prostaglandin F2a and a GnRH-agonist (2011)
  • Author(s): Miyabi Ohmura, et al
  • Journal Title: The Veterinary Record Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Effect of IL-12 on the canine dendritic cell maturation following differentiation induced by granulocyte-macrophage CSF and IL-4 (2010)
  • Author(s): Sugiura K, Wijewardana V, Fujimoto M, Akazawa T, Yahata M, Mito K, Hatoya S, Inoue N, Inaba T
  • Journal Title: Vet. Immunol. Immunopathol Volume: 137巻 Issue: 3-4 Pages: 322-326
  • DOI: 10.1016/j.vetimm.2010.06.006
  • Peer Reviewed
• [Journal Article] Detection of Relaxin mRNA in the Corpus Luteum, Uterus, and Uterine Cervix in the Bitch (2010)
  • Author(s): Tamada H, Kawate N, Kawata N, Inaba T, Kida K, Hatoya S, Akune A, Nakama K, Kohsaka T, Sawada T
  • Journal Title: Journal of Veterinary Medical Science Volume: 72 Issue: 10 Pages: 1383-1386
  • DOI: 10.1292/jvms.09-0485
  • NAID: 130000264202
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [Journal Article] INFγmarkedly cooperates with intratumoral dendritic cell vaccine in dog tumor models (2010)
  • Author(s): Mito K, Sugiura K, Ueda K, Hori T, Akazawa T, Yamate J, Hatoya S, Inaba M, Inoue N, Ikehara S, Inaba T
  • Journal Title: Cancer Res Volume: 70巻 Issue: 18 Pages: 7093-7101
  • DOI: 10.1158/0008-5472.can-10-0600
  • Peer Reviewed
• [Journal Article] Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo (2010)
  • Author(s): Kioka N, Ito T, Yamashita H, Uekawa N, Umemoto T, Motoyoshi S, Imai H, Takahashi K, Watanabe H, Yamada M, Ueda K
  • Journal Title: Exp. Cell Res Volume: 316巻 Issue: 10 Pages: 1728-1738
  • DOI: 10.1016/j.yexcr.2010.03.019
  • Peer Reviewed
• [Journal Article] Effect of IL-12 on the canine dendritic cell maturation following differentiation induced by granulocyte-macrophage CSF and IL-4 (2010)
  • Author(s): Kikuya Sugiura, et al
  • Journal Title: Veterinary Immunology and Immunopathology Volume: 137 Pages: 322-326
  • Peer Reviewed
• [Presentation] イヌにおけるマウスES細胞様のiPS細胞の誘導 (2012)
  • Author(s): 今井裕
  • Organizer: 第137回日本生殖医学会関西支部集談会
  • Place of Presentation: 大阪
  • Year and Date: 2012-03-03
• [Presentation] イヌにおけるマウスES細胞様のiPS細胞の誘導 (2012)
  • Author(s): 今井裕, ら
  • Organizer: 第137回日本生殖医学会関西支部集談会
  • Place of Presentation: ハービスPLAZA(大阪)
  • Year and Date: 2012-03-03
• [Presentation] イヌES細胞の研究から再生獣医療に向けて (2012)
  • Author(s): 稲葉俊夫
  • Organizer: 第17回滋賀県獣医学会
  • Place of Presentation: 滋賀
  • Year and Date: 2012-02-26
• [Presentation] イヌES細胞の研究から再生獣医療に向けて (2012)
  • Author(s): 稲葉俊夫
  • Organizer: 第17回滋賀県獣医学会
  • Place of Presentation: 瀬田アーバンホテル(滋賀)(招待講演)
  • Year and Date: 2012-02-26
• [Presentation] Establishment of canine induced pluripotent stem cells using retro virus and maintenance of their pluripotency in culture (2011)
  • Author(s): 今井裕
  • Organizer: 第2回国際繁殖生物学会
  • Place of Presentation: ケアンズ(豪州)
  • Year and Date: 2011-10-09
• [Presentation] Establishment of canine induced pluripotent stem cells using retro virus and maintenance of their pluripotency in culture (2011)
  • Author(s): 今井裕, ら
  • Organizer: 第2回国際繁殖生物学会
  • Place of Presentation: ケアンズ・コンベンションセーンター(豪州)
  • Year and Date: 2011-10-09
• [Presentation] イヌ骨髄間質細胞の神経幹細胞に及ぼす影響 (2011)
  • Author(s): 稲葉俊夫
  • Organizer: 第152回日本獣医学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2011-09-20
• [Presentation] イヌ骨髄間質細胞の神経幹細胞に及ぼす影響 (2011)
  • Author(s): 稲葉俊夫, ら
  • Organizer: 第152回日本獣医学会学術集会
  • Place of Presentation: 大阪府立大学(大阪)
  • Year and Date: 2011-09-20
• [Presentation] イヌ顆粒球減少症に向けたイヌ造血因子の作製 (2011)
  • Author(s): 稲葉俊夫
  • Organizer: 第152回日本獣医学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2011-09-19
• [Presentation] イヌにおける人工多能性幹細胞樹立の試み (2011)
  • Author(s): 今井裕
  • Organizer: 第136回日本生殖医学会関西支部集談会
  • Place of Presentation: 大阪
  • Year and Date: 2011-03-05
• [Presentation] イヌにおける人工多能性幹細胞樹立の試み (2011)
  • Author(s): 今井裕, ら
  • Organizer: 第136回日本生殖医学会関西支部集談会
  • Place of Presentation: ハービスPLAZA(大阪)
  • Year and Date: 2011-03-05
• [Presentation] サルES細胞からのオリゴデンドロサイトへの簡便な分化誘導法 (2010)
  • Author(s): 稲葉俊夫
  • Organizer: 第150回日本獣医学会学術集会
  • Place of Presentation: 北海道
  • Year and Date: 2010-09-16
• [Presentation] サルES細胞からのオリゴデンドロサイトへの簡便な分化誘導法 (2010)
  • Author(s): 稲葉俊夫, ら
  • Organizer: 日本獣医学会第150回大会
  • Place of Presentation: 帯広畜産大学(北海道)
  • Year and Date: 2010-09-16
• [Remarks]
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• [Remarks]
  • URL: http://kyoindb.acs.osakafu-u.ac.jp/profile/out.cudjDYHfHMO.PEVGDxV-iw==.html
• [Remarks]
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