A Establishment of a leukemina model of cynomolgus macaque

• Project/Area Number: 23790442
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: ISHIGAKI Hirohito 滋賀医科大学, 医学部, 助教 (90432301)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: iPS細胞 / 白血病 / 動物モデル / 動物実験モデル / カニクイザル / 白血病幹細胞 / レトロウイルス / 再生医療 / 主要組織適合抗原

Research Abstract

We successfully induced CD34 positive hematopoietic stem cells (iCD34) from induced pluripotent stem cells (iPS cells) of a cynomolgus macaque which homozygously have a certain haplotype of major histocompatibility complex (Mafa-HT1). Next, we transduced well-known leukemic genes, AML1/ETO and FLT3mutant, or BCR/ABL, to the iCD34 by retrovirus. These two types of iCD34 (leukemic iCD34) cells with the leukemic genes could form many colonies in methylcellulose media and be cultured for long term without any cytokines. These leukemic iCD34 could be alive in NOD/Shi-scid, IL-2Rγnull mouse (NOG mouse) after intrabonemarrow-bonemarrow transplantation (IBM-BMT). We are preparing experiments in which a bonemarrow transplantation of the leukemic iCD34 with AML1/ETO+FLT3mutant to a cynomolgusmacaque with heterogygous MHC.

Research Products

• [Journal Article] Memory immune responses against pandemic (H1N1) 2009 influenza virus induced by a whole particle vaccine in cynomolgus monkeys carrying Mafa-A*052:02 (2012)
  • Author(s): Arikata M, Itoh Y, Okamatsu M, Maeda T, Shiina T, Tanaka K, Suzuki S, Nakayama M, Sakoda Y, Ishigaki H, Takada A, Ishida H, Soda K, Pham VL, Tsuchiya H, Nakamura S, Torii R, Shimizu T, Inoko H, Ohkubo I, Kida H, Ogasawara K.
  • Journal Title: PLos ONE Volume: 7
  • Peer Reviewed
• [Journal Article] Expression of megakaryocytic and myeloid markers in blasts of transient abnormal myelopoiesis in a stillbirth with Down syndrome: report of histopathological findings of an autopsy case (2011)
  • Author(s): Ishigaki, H, Miyauchi J, Yokoe A, Nakayama M, Yanagi T, Taga T, Ohta S, Itoh Y, Ogasawara K
  • Journal Title: Human Pathol. Volume: 42 Pages: 141-145
  • Peer Reviewed
• [Journal Article] Efficacy of single intravenous injection of peramivir against influenza B virus infection in ferrets and cynomolgus macaques (2011)
  • Author(s): Kitano M, Itoh Y, Kodama M, Ishigaki H, Nakayama M, Ishida H, Baba K, Noda T, Sato K, Nihashi Y, Kanazu T, Yoshida R, Torii R, Sato A, Ogasawara K
  • Journal Title: Antimicrobial Agents and Chemotherapy Volume: Vol.55 Issue: 11 Pages: 4961-4970
  • DOI: 10.1128/aac.00412-11
  • Peer Reviewed
• [Presentation] カニクイザル iPS 細胞由来癌細胞株を用いた、担癌カニクイザルモデルの作製 (2013)
  • Author(s): 石垣宏仁、仲山美沙子、伊藤靖、小笠原一誠
  • Organizer: 第102回病理学会総会
  • Place of Presentation: 札幌
• [Book] フトによる自然免疫の増強、臨床免疫 (2011)
  • Author(s): 片桐洋子、石垣宏仁、清河信敬
  • Publisher: アレルギー科
• [Remarks]
  • URL: http://www.shiga-med.ac.jp/~hqpatho2/