Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2014

  　

  　

  Sapporo Medical University   Graduate School of Medicine   大学院生

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Neurosurgery  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• 札幌医科大学附属病院   産科周産期科   助教  

• 神経再生医療学部門   共同研究者  

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• Intravenous infusion of exosome for the treatment of neonatal hypoxic ischemic encephalopathy

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2023.04

  -

  2026.03

   

  寺田 光次郎, 津川 毅, 飯塚 裕典, 佐々木 祐典, 長濱 宏史, 坂井 拓朗, 本望 修

• Mesenchymal stem cells for brain injury of prematurity in a rat model.

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2020.04

  -

  2023.03

   

  寺田 光次郎, 川崎 幸彦, 佐々木 祐典, 福村 忍, 小林 正樹, 坂井 拓朗, 本望 修, 飯塚 裕典

  　View Summary

  我々は、予備実験において、胎生18日目の妊娠SDラット（妊娠期間：21日）に対して、エンドトキシンであるリポポリサッカライド（LPS）を腹腔内投与し、出生した日齢7の新生仔ラットに左総頚動脈結紮・低酸素暴露をすることで、脳室周囲の白質に虚血領域を呈する脳室周囲白質軟化症（Periventricular leukomalacia：PVL）モデルラットを作成した。PVLモデルラットは、低酸素虚血単独群（左総頚動脈結紮・低酸素暴露のみ、母体LPSなし）と比較して、大脳の虚血容積が増大し、重症になることが判明した。 本研究では、PVLモデルラットに対して、別の成体ラットより採取、培養した骨髄間葉系幹細胞（Mesenchymal stem cell：MSC）を経静脈的に投与し、急性期MSCの治療効果と作用メカニズム、特に発達脳における神経保護効果や神経可塑性の亢進について検証している。 日齢10のPVLモデルラットを、MSC群とVehicle群に振り分け、MSCまたはDMEM（培養液のみ、細胞なし）を経静脈的に投与した。運動機能の評価としてロータロッド試験、シリンダー試験、空間認知機能の評価としてモリス水迷路試験を用いて行動学的解析を実施した。これまでに、MSC群で良好な結果が得られており、MSC治療の有効性を確認した。また動物用7T-MRIを用いて、MSC投与前後における大脳の虚血体積および残存大脳容積、脳血流の変化について検証した。観察期間終了後の脳組織を用いて、拡散テンソル画像による神経線維の評価、免疫化学染色による神経細胞や脳の髄鞘化の動向について検証している。

• The development of novel therapies for intractable epilepsy with bone marrow mesenchymal stem cells

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2016.04

  -

  2019.03

   

  Fukumura Shinobu

  　View Summary

  The present study tested the hypothesis that systemically infused mesenchymal stem cells (MSCs) reduce epileptogenesis by inhibiting neuronal cell death and suppressing aberrant MFS, leading to preservation of cognitive function in a rat model of epilepsy. Status epilepticus (SE) was induced using the lithium-pilocarpine injection. MSC infusion inhibited epileptogenesis and preserved cognitive function after SE. The infused MSCs preserved GAD67+ and NeuN+ hippocampal neurons. Furthermore, the MSC infusion suppressed the aberrant MFS in the hippocampus as evidenced by manganese enhanced MRI and Timm staining. This study demonstrated that the intravenous infusion of MSCs mitigated epileptogenesis, thus advancing MSCs as an effective approach for epilepsy in clinical practice.

• Therapeutic Effects of Intravenous Infusion of MSCs in Hypoxic-Ischemic Encephalopathy Rat

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2014

  -

  2016

   

  Sakai Takuro, HONMOU Osamu

  Authorship： Principal investigator

  　View Summary

  We aimed to investigate the effect of mesenchymal stem cells (MSCs) transplantation in a rat model of neonatal hypoxic-ischemic encephalopathy (HIE) by histological, MRI, and behavioral analysis. At postnatal day 7, rats were underwent HI by left common carotid artery occlusion followed by 120 min hypoxia (8% oxygen). At postnatal day 10, transplantation of MSCs was performed by intravenous injection. Compared with the vehicle (control) group, the MSC infused group showed a significant improvement in athletic performance by the evaluation with the beam walk test. The MRI also demonstrated that the MSC infused group showed a significant reduction of the ischemic volume compared to the vehicle group. Collectively, intravenous infusion of MSCs might provide therapeutic efficacy in a rat model of HIE.

• Functional recovery following intravenous infusion of MSCs via repair of pericytes in rat spinal cord injury

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2013.04

  -

  2016.03

   

  Sasaki Masanori, Wanibuchi Masahiko, Mikami Takeshi, Kobayashi Masaki, Nakazaki Masahito, Sakai Takuro, Sasaki Yuichi, Suzuki Junpei, Morita Tomonori, Namioka Ai, Namioka Takahiro

  　View Summary

  Mesenchymal stem cells (MSCs) derived from bone marrow may represent a potential source for organ regeneration via multiple mechanisms based on animal experiments. In this study, we induced a contusive SCI at T9 in the rat and studied the effects of intravenous MSC infusion on blood spinal cord barrier (BSCB) permeability, microvascular architecture and locomotor recover. Spatial and temporal changes in BSCB integrity were assessed by intravenous infusions of Evans blue (EvB). SCI resulted in prolonged BSCB leakage that was most severe at the impact site but disseminated extensively rostral and caudal to the lesion. Contused spinal cords also showed an increase in microvasculature. In MSC-treated rats, BSCB leakage was reduced, and locomotor function improved after MSC infusion. These results suggest that intravenously delivered MSCs have important effects on reducing BSCB leakage which could contribute to their therapeutic efficacy.

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