Induction of neural cells with spinal motoneuron phenotype from human iPS cells and the transplantation to totally transected spinal cords in mice

• Iinuma Masahiro

  Department of Regenerative Medicine, St. Marianna University Graduate School of Medicine, Kawaksaki, Kanagawa, Japan Department of Immunology and Medicine, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan Department of Orthopedics, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan

• Umehara Tasuku

  Department of Regenerative Medicine, St. Marianna University Graduate School of Medicine, Kawaksaki, Kanagawa, Japan Department of Immunology and Medicine, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan Department of Orthopedics, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan

• Arimitsu Nagisa

  Department of Regenerative Medicine, St. Marianna University Graduate School of Medicine, Kawaksaki, Kanagawa, Japan Department of Immunology and Medicine, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan

• Shimizu Jun

  Department of Regenerative Medicine, St. Marianna University Graduate School of Medicine, Kawaksaki, Kanagawa, Japan Department of Immunology and Medicine, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan

• Misawa Hiroko

  Department of Regenerative Medicine, St. Marianna University Graduate School of Medicine, Kawaksaki, Kanagawa, Japan Department of Immunology and Medicine, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan Department of Orthopedics, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan

• Takai Kenji

  Department of Regenerative Medicine, St. Marianna University Graduate School of Medicine, Kawaksaki, Kanagawa, Japan Department of Immunology and Medicine, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan

• Fujiwara Naruyoshi

  Department of Regenerative Medicine, St. Marianna University Graduate School of Medicine, Kawaksaki, Kanagawa, Japan Department of Immunology and Medicine, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan

• Fujii Atsushi

  Department of Regenerative Medicine, St. Marianna University Graduate School of Medicine, Kawaksaki, Kanagawa, Japan Department of Immunology and Medicine, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan Department of Orthopedics, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan

• Ueda Yuji

  Department of Regenerative Medicine, St. Marianna University Graduate School of Medicine, Kawaksaki, Kanagawa, Japan Department of Immunology and Medicine, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan

• Wakisaka Sueshige

  Department of Regenerative Medicine, St. Marianna University Graduate School of Medicine, Kawaksaki, Kanagawa, Japan Department of Immunology and Medicine, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan

• Suzuki Tomoko

  Department of Regenerative Medicine, St. Marianna University Graduate School of Medicine, Kawaksaki, Kanagawa, Japan Department of Immunology and Medicine, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan

• Hirotsu Chieko

  Department of Regenerative Medicine, St. Marianna University Graduate School of Medicine, Kawaksaki, Kanagawa, Japan Department of Immunology and Medicine, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan

• Beppu Moroe

  Department of Orthopedics, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan

• Suzuki Noboru

  Department of Regenerative Medicine, St. Marianna University Graduate School of Medicine, Kawaksaki, Kanagawa, Japan Department of Immunology and Medicine, St. Marianna University School of Medicine, Kawaksaki, Kanagawa, Japan

抄録

Transplantation of neural cells is a promising therapeutic strategy for spinal cord injury (SCI). Here we generated neurons including those with spinal motoneuron phenotype from human induced pluripotent stem (hiPS) cells by leading to formation of embryoid bodies (EB) and subsequent adherent culture for 4 days during which retinoic acid (RA), noggin (NOG) and sonic hedgehog (SHH) were introduced twice. Spinal motoneuron specific HB9 mRNA expression remarkably increased in the presence of RA, NOG and SHH. With this culture condition, the neurons expressed neurofilament middle chain (NFM), βIII tubulin and HB9 proteins in vitro.<BR>We then transplanted the hiPS derived human neurons into SCI mice with complete transection of Th11. Motor function of neuron transplanted SCI mice was significantly improved compared with those of vehicle injected SCI mice. Grafted cells survived and expressed βIII tubulin and HB9 diffusely 36 days after the transplantation. Galactocerebroside positive cells increased and glial fibrillary acidic protein (GFAP) expression reduced in the transection site of neuron transplanted SCI mice.<BR>The grafted motoneurons elongated human neural cell adhesion molecule (hNCAM) positive axons over the L1 spinal level. NCAM positive axons at L1 carried a neuron tracer cholera toxin β subunit (CTβ), which had been injected into Th10 of spinal cord, cranial region of the SCI/motoneuron grafted site (Th11).<BR>Collectively we succeeded in generating neurons which include those with HB9 positive spinal motoneuron phenotype from hiPS cells. The neurons brought about restoration of the motor function and histological improvement in an SCI.

収録刊行物

• Inflammation and Regeneration

  Inflammation and Regeneration 35 (3), 154-163, 2015

  一般社団法人 日本炎症・再生医学会

キーワード

• neural regeneration
• human iPS cells
• spinal motor neuron
• spinal cord injury
• HB9

詳細情報

• CRID: 1390001205256544896
• NII論文ID: 130005078573
• DOI: 10.2492/inflammregen.35.154
• ISSN: 18808190
• ISSN: 18809693
• Web Site: https://search.jamas.or.jp/link/ui/2016247037
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可