Development of Cord Blood Transplantation Therapy with Autism Model Marmosets

• Project/Area Number: 20K07752
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Ichinohe Noritaka 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 微細構造研究部, 部長 (00250598)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 血液幹細胞 / 間葉系幹細胞 / 幹細胞移植治療 / 自閉症 / マーモセット / 培養 / フローサイトメトリー / 治療法 / 幹細胞培養 / 骨髄 / 幹細胞

Outline of Research at the Start

自閉症スペクトラム障害（ASD）は全人口の1-3%存在すると言われ、そのコア症状である社会性の障害と極端な固執性のために社会的適応に大きな困難さを持つ。しかし、現在のところ明らかに効果のある治療法は未だ存在せず、新たな有効な治療法が切望されている。当該ASDモデルマーモセットは、ミクログリアの異常、炎症関連遺伝子の発現異常など、ヒトと同様な免疫異常が見られ、臍帯血移植のASDの治療効果の評価、その機序、臍帯血由来のどの細胞に有効性があるかを評価する。

Outline of Final Research Achievements

Marmoset mesenchymal stem cells (MSCs) were digested and isolated using trypsin after removal of femoral and humeral marrow and maintained in 15% FBS IMDM or StemPro MSC SFM (Gibco) without growth factors. When the medium was replaced, only cells that remained attached to the culture substrate were further cultured. Cultured cells were spindle-shaped and resembled fibroblasts characteristic of MSCs. FACS analysis of cultured cells showed an average of 80% CD90-positive cells and 35% CD73-positive cells, specific markers for MSCs; cell immunological staining with the MSC-specific antibodies CD90 and CD105 yielded positive results.

Academic Significance and Societal Importance of the Research Achievements

本研究は、自閉症治療への新たなアプローチを模索するものである。霊長類マーモセットは、げっ歯類よりもヒトの自閉症モデルとして優れている。現在注目されている自閉症の治療法として血液・間葉系幹細胞移植があるが、これを実現するためには、マーモセットを用いたモデルでの治療法開発が不可欠である。我々の研究では、マーモセットからの造血幹細胞、間葉系幹細胞の分離、培養が可能であることを証明した。これにより、自閉症モデル動物への治療法開発目的移植が可能となった。これは自閉症治療における新たな視点となると考えられる。

Research Products

• [Journal Article] Prenatal valproic acid-induced autism marmoset model exhibits higher salivary cortisol levels (2022)
  • Author(s): Nakamura, M., Nakagami, A., Nakagaki, K., Yasue, M., Kawai, N., & Ichinohe, N
  • Journal Title: Front Behav Neurosci Volume: 16 Pages: 943759-943759
  • DOI: 10.3389/fnbeh.2022.943759
  • Peer Reviewed
• [Journal Article] Reduced childhood social attention in autism model marmosets predicts impaired social skills and inflexible behavior in adulthood (2022)
  • Author(s): Nakagami, A., Yasue, M., Nakagaki, K., Nakamura, M., Kawai, N., & Ichinohe, N
  • Journal Title: Front Psychiatry Volume: 13 Pages: 885433-885433
  • DOI: 10.3389/fpsyt.2022.885433
  • Peer Reviewed / Open Access
• [Journal Article] Association between vascular endothelial growth factor-mediated blood-brain barrier dysfunction and stress-induced depression (2022)
  • Author(s): Hitomi Matsuno, Shoko Tsuchimine, Kazunori O'Hashi, Kazuhisa Sakai, Kotaro Hattori, Shinsuke Hidese, Shingo Nakajima, Shuichi Chiba, Aya Yoshimura, Noriko Fukuzato, Mayumi Kando, Megumi Tatsumi Shintaro Ogawa, Noritaka Ichinohe, Hiroshi Kunugi, and Kazuhiro Sohya
  • Journal Title: Molecular Psychiatry Volume: - Issue: 9 Pages: 3822-3832
  • DOI: 10.1038/s41380-022-01618-3
  • Peer Reviewed
• [Journal Article] Brain Dp140 alters glutamatergic transmission and social behaviour in the mdx52 mouse model of Duchenne muscular dystrophy (2022)
  • Author(s): Hashimoto Yasumasa、Kuniishi Hiroshi、Sakai Kazuhisa、Fukushima Yuta、Du Xuan、Yamashiro Kunihiko、Hori Kei、Imamura Michihiro、Hoshino Mikio、Yamada Mitsuhiko、Araki Toshiyuki、Sakagami Hiroyuki、Takeda Shin’ichi、Itaka Keiji、Ichinohe Noritaka、Muntoni Francesco、Sekiguchi Masayuki、Aoki Yoshitsugu
  • Journal Title: Progress in Neurobiology Volume: 216 Pages: 102288-102288
  • DOI: 10.1016/j.pneurobio.2022.102288
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cortical neural dynamics unveil the rhythm of natural visual behavior in marmosets (2022)
  • Author(s): Kaneko Takaaki、Komatsu Misako、Yamamori Tetsuo、Ichinohe Noritaka、Okano Hideyuki
  • Journal Title: Communications Biology Volume: 5 Issue: 1 Pages: 1-13
  • DOI: 10.1038/s42003-022-03052-1
  • Peer Reviewed / Open Access
• [Journal Article] Functional and molecular characterization of a non-human primate model of autism spectrum disorder shows similarity with the human disease (2021)
  • Author(s): Satoshi Watanabe, Tohru Kurotani, Tomofumi Oga , Jun Noguchi, Risa Isoda, Akiko Nakagami,Kazuhisa Sakai, Keiko Nakagaki, Kayo Sumida, Kohei Hoshino , Koichi Saito, Izuru Miyawaki,Masayuki Sekiguchi, Keiji Wada, Takafumi Minamimoto & Noritaka Ichinohe
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 5388-5388
  • DOI: 10.1038/s41467-021-25487-6
  • Peer Reviewed
• [Journal Article] DDAH1 as a novel regulator of oligodendrocyte differentiation in the central nervous system remyelination (2021)
  • Author(s): Akiko Uyeda, Quan Lili, Yuki Kato, Nagaaki Muramatsu, Shogo Tanabe, Kazuhisa Sakai, Noritaka Ichinohe, Yukio Kawahara, Tatsunori Suzuki and Rieko Muramatsu
  • Journal Title: GLIA Volume: 69 Issue: 11 Pages: 2591-2604
  • DOI: 10.1002/glia.24060
  • Peer Reviewed
• [Journal Article] Structure and function of neural circuit related to gloss perception in the macaque inferior temporal cortex: a case report (2021)
  • Author(s): Komatsu Hidehiko、Nishio Akiko、Ichinohe Noritaka、Goda Naokazu
  • Journal Title: Brain Structure and Function Volume: 226 Issue: 9 Pages: 3023-3030
  • DOI: 10.1007/s00429-021-02324-6
  • Peer Reviewed / Open Access