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• 2002年

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  2006年

  札幌医科大学   大学院医学研究科  

• 1995年

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  2001年

  札幌医科大学   医学部  

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• 2023年04月

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  継続中

  札幌医科大学   医学部 附属フロンティア医学研究所 神経再生医療学部門   講師

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• ライフサイエンス   脳神経外科学  

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• 札幌医科大学   医学部付属フロンティア研究所神経再生医療学部門   講師  

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• Therapeutic efficacy of intravenous infusion of mesenchymal stem cells in rat perinatal brain injury.

  Kojiro Terada, Masanori Sasaki, Hiroshi Nagahama, Yuko Kataoka-Sasaki, Shinichi Oka, Ryo Ukai, Takahiro Yokoyama, Yusuke Iizuka, Takuro Sakai, Shinobu Fukumura, Takeshi Tsugawa, Jeffery D Kocsis, Osamu Honmou

  Pediatric research    2023年07月  [国際誌]

  　概要を見る

  BACKGROUND: Perinatal brain injury is multifactorial and primarily associated with brain prematurity, inflammation, and hypoxia-ischemia. Although recent advances in perinatal medicine have improved the survival rates of preterm infants, neurodevelopmental disorders remain a significant complication. We tested whether the intravenous infusion of mesenchymal stem cells (MSCs) had therapeutic efficacy against perinatal brain injury in rats. METHODS: Pregnant rats at embryonic day (E) 18 received lipopolysaccharide and the pups were born at E21. On postnatal day (PND) 7, the left common carotid artery of each pup was ligated, and they were exposed to 8% oxygen for 2 h. They were randomized on PND10, and MSCs or vehicle were intravenously infused. We performed behavioral assessments, measured brain volume using MRI, and performed histological analyses on PND49. RESULTS: Infused MSCs showed functional improvements in our model. In vivo MRI revealed that MSC infusion increased non-ischemic brain volume compared to the vehicle group. Histological analyses showed that cortical thickness, the number of NeuN+ and GAD67+ cells, and synaptophysin density in the non-ischemic hemisphere in the MSC group were greater than the vehicle group, but less than the control group. CONCLUSIONS: Infused MSCs improve sensorimotor and cognitive functions in perinatal brain injury and enhance neuronal growth. IMPACT: Intravenous infusion of MSCs improved neurological function in rats with perinatal brain injury, including motor, sensorimotor, cognitive, spatial, and learning memory. Infused MSCs increased residual (non-ischemic) tissue volume, number of neuronal cells, GABAergic cells, and cortical synapses in the contralesional (right) hemisphere. Intravenous administration of MSC might be suitable for the treatment of perinatal brain injury.

  DOI PubMed

• A practical protocol for high-spatial-resolution magnetic resonance angiography for cerebral arteries in rats.

  Hiroshi Nagahama, Masanori Sasaki, Katsuya Komatsu, Kaori Sato, Yoshimi Katagiri, Masaki Kamagata, Yuko Kataoka-Sasaki, Shinichi Oka, Ryo Ukai, Takahiro Yokoyama, Kojiro Terada, Masato Kobayashi, Jeffery D Kocsis, Osamu Honmou

  Journal of neuroscience methods   386   109784 - 109784  2023年01月  [国際誌]

  　概要を見る

  BACKGROUND: Magnetic resonance angiography (MRA) is an important tool in rat models of cerebrovascular disease. Although MRA has long been used in rodents, the image quality is typically not as high as that observed in clinical practice. Moreover, studies on MRA image quality in rats are limited. This study aimed to develop a practical high-spatial-resolution MRA protocol for imaging cerebral arteries in rats. NEW METHOD: We used the "half position method" regarding coil placement and modified the imaging parameters and image reconstruction method. We applied this new imaging method to measure maturation-related signal changes on rat MRAs. RESULTS: The new practical high-spatial-resolution MRA imaging protocol obtained a signal intensity up to 3.5 times that obtained using a basic coil system, simply by modifying the coil placement method. This method allowed the detection of a gradual decrease in the signal in cerebral vessels with maturation. COMPARISON WITH EXISTING METHODS: A high-spatial-resolution MRA for rats was obtained with an imaging time of approximately 100 min. Comparable resolution and image quality were obtained using the new protocol with an imaging time of 30 min CONCLUSIONS: The new practical high-spatial-resolution MRA protocol can be implemented simply and successfully to achieve high image quality with an imaging time of approximately 30 min. This protocol will benefit researchers performing MRA imaging in cerebral artery studies in rats.

  DOI PubMed

• Enhanced Network in Corticospinal Tracts after Infused Mesenchymal Stem Cells in Spinal Cord Injury.

  Ryosuke Hirota, Masanori Sasaki, Yuko Kataoka-Sasaki, Tsutomu Oshigiri, Kota Kurihara, Ryunosuke Fukushi, Shinichi Oka, Ryo Ukai, Mitsunori Yoshimoto, Jeffery D Kocsis, Toshihiko Yamashita, Osamu Honmou

  Journal of neurotrauma   39 ( 23-24 ) 1665 - 1677  2022年12月  [国際誌]

  　概要を見る

  Although limited spontaneous recovery occurs after spinal cord injury (SCI), current knowledge reveals that multiple forms of axon growth in spared axons can lead to circuit reorganization and a detour or relay pathways. This hypothesis has been derived mainly from studies of the corticospinal tract (CST), which is the primary descending motor pathway in mammals. The major CST is the dorsal CST (dCST), being the major projection from cortex to spinal cord. Two other components often called "minor" pathways are the ventral and the dorsal lateral CSTs, which may play an important role in spontaneous recovery. Intravenous infusion of mesenchymal stem cells (MSCs) provides functional improvement after SCI with an enhancement of axonal sprouting of CSTs. Detailed morphological changes of CST pathways, however, have not been fully elucidated. The primary objective was to evaluate detailed changes in descending CST projections in SCI after MSC infusion. The MSCs were infused intravenously one day after SCI. A combination of adeno-associated viral vector (AAV), which is an anterograde and non-transsynaptic axonal tracer, was injected 14 days after SCI induction. The AAV with advanced tissue clearing techniques were used to visualize the distribution pattern and high-resolution features of the individual axons coursing from above to below the lesion. The results demonstrated increased observable axonal connections between the dCST and axons in the lateral funiculus, both rostral and caudal to the lesion core, and an increase in observable axons in the dCST below the lesion. This increased axonal network could contribute to functional recovery by providing greater input to the spinal cord below the lesion.

  DOI PubMed

• Intravenous Infusion of Autoserum-Expanded Autologous Mesenchymal Stem Cells in Patients With Chronic Brain Injury: Protocol for a Phase 2 Trial.

  Shinichi Oka, Tomohiro Yamaki, Masanori Sasaki, Ryo Ukai, Mitsuhiro Takemura, Takahiro Yokoyama, Yuko Kataoka-Sasaki, Rie Onodera, Yoichi M Ito, Shigeki Kobayashi, Jeffery D Kocsis, Yasuo Iwadate, Osamu Honmou

  JMIR research protocols   11 ( 7 ) e37898  2022年07月  [国際誌]

  　概要を見る

  BACKGROUND: Brain injuries resulting from motor vehicle accidents and falls, as well as hypoxic insults and other conditions, are one of the leading causes of disability and death in the world. Current treatments are limited but include continuous rehabilitation, especially for chronic brain injury. Recent studies have demonstrated that the intravenous infusion of mesenchymal stem cells (MSCs) has therapeutic efficacy for several neurological diseases, including stroke and spinal cord injury. OBJECTIVE: The objective of our investigator-initiated clinical trial is to assess the safety and potential efficacy of the intravenous infusion of autoserum-expanded autologous MSCs for patients with chronic brain injury. METHODS: The (phase 2) trial will be a single-arm, open-label trial with the primary objective of confirming the safety and efficacy of autoserum-expanded autologous MSCs (STR-01; produced under good manufacturing practices) when administered to patients with chronic brain injury. The estimated number of enrolled participants is 6 to 20 patients with a modified Rankin Scale grade of 3 to 5. The assessment of safety and the proportion of cases in which the modified Rankin Scale grade improves by 1 point or more at 180 days after the injection of STR-01 will be performed after MSC infusion. RESULTS: We received approval for our clinical trial from the Japanese Pharmaceuticals and Medical Devices Agency on December 12, 2017. The trial will be completed on June 11, 2023. The registration term is 5 years. The recruitment of the patients for this trial started on April 20, 2018, at Sapporo Medical University Hospital in Japan. CONCLUSIONS: Our phase 2 study will aim to address the safety and efficacy of the intravenous infusion of MSCs for patients with chronic brain injury. The use of STR-01 has been performed for patients with cerebral infarction and spinal cord injury, providing encouraging results. The potential therapeutic efficacy of the systemic administration of autoserum-expanded autologous MSCs for chronic brain injury should be evaluated, given its safety and promising results for stroke and spinal cord injury. TRIAL REGISTRATION: Japan Medical Association Center for Clinical Trials JMA-IIA00333; https://tinyurl.com/nzkdfnbc. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37898.

  DOI PubMed

• Pharmacological Difference Between Platelet Aggregations in Cardioembolic Stroke Patients with Direct Oral Anticoagulants: A Pilot Study.

  Masahito Nakazaki, Shinichi Oka, Hirotoshi Magota, Ryo Kiyose, Rie Onodera, Ryo Ukai, Yuko Kataoka-Sasaki, Masanori Sasaki, Osamu Honmou

  Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association   31 ( 7 ) 106520 - 106520  2022年07月  [国際誌]

  　概要を見る

  Background Selecting the appropriate direct oral anticoagulants (DOACs) for embolic ischemic stroke patients, especially on concurrent antiplatelet therapy, is important. However, a limited number of studies have reported on the pharmacological differences in platelet aggregation of each DOAC. We aimed to evaluate the antiplatelet effects of selected DOACs, by comparing dabigatran (a direct oral thrombin inhibitor) and factor Xa (FXa) inhibitors (apixaban and rivaroxaban) in patients who had suffered a cardioembolic stroke. Methods We retrospectively evaluated 12 patients diagnosed with a cardioembolic stroke who took any DOAC without an antiplatelet drug and underwent platelet aggregation tests within 60 days from the onset of symptoms. The platelet aggregation tests were analyzed by both light transmission aggregometry and VerifyNow®. Results Six patients (50%) took dabigatran, while the other six (50%) took an FXa inhibitor (n = 4 for apixaban and n = 2 for rivaroxaban). From the light transmission aggregometry analysis, it was found that the maximal extent of aggregation for adenosine diphosphate (ADP) was significantly higher with dabigatran than with FXa inhibitors, and the ED50 value of ADP on platelet aggregation was significantly lower with dabigatran than with FXa inhibitors. Moreover, the VerifyNow® analyses revealed that P2Y12 reaction units were significantly higher with dabigatran than with FXa inhibitors. Conclusions Dabigatran had little impact on platelet aggregation compared to FXa inhibitors in patients who had suffered a cardioembolic stroke with atrial fibrillation, and who took DOACs for secondary prevention within 60 days from the onset.

  DOI PubMed

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共同研究・競争的資金等の研究課題 【 表示 ／ 非表示 】

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• 脳梗塞と脊髄損傷に対する中枢神経系全域の可塑性賦活化による治療戦略の検討

  基盤研究(B)

  研究期間:

  2022年04月

  -

  2025年03月

   

  本望 修, 佐々木 祐典, 鵜飼 亮, 岡 真一, 佐々木 優子

• 健康寿命延長に関与する骨髄幹細胞の自己治癒能と全身の恒常性維持

  基盤研究(C)

  研究期間:

  2022年04月

  -

  2025年03月

   

  佐々木 優子, 佐々木 祐典, 鵜飼 亮, 岡 真一, 本望 修

• 脳梗塞に対する次世代型エクソソームを用いた革新的治療法の開発

  基盤研究(C)

  研究期間:

  2022年04月

  -

  2025年03月

   

  鵜飼 亮, 佐々木 祐典, 本望 修

• 脊髄損傷に対する骨髄間葉系幹細胞移植による、脳脊髄での可塑性亢進メカニズムの解析

  基盤研究(C)

  研究期間:

  2021年04月

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  2024年03月

   

  岡 真一, 佐々木 祐典, 横山 貴裕, 本望 修, 鵜飼 亮

  　研究概要を見る

  令和3年度、当院にMSC治療を目的に入院した脊髄損傷症例は、おおよそ20例を数え、順調に症例数を積み重ねている状況である。全ての脊髄損傷症例の脳、脊髄のMRIデータを検証した。撮像時期は、原則、入院時、投与直前、 投与1ヶ月後、投与3ヶ月後、投与6ヶ月後の時点としていたかが、投与条件に当てはまらず投与を受けなかった症例や入院病床の調整の関係で、MRIの撮像を出来ない症例も散見された。特に脳DTIデータを用いたコネクトーム解析では、標準化の方法、使用する脳atlasの選択、ROI間の接続強度の閾値設定など、症例間でばらつきのない均一な解析を実施するためのパラメータの設定の検討を引き続き実施している。さらに、T1WI、T2WIなどを用いて大脳皮質厚や体積などの構造学的なデータ解析も同時に実施し、コネクトーム解析で得られた結果との比較も実施している。また、脊髄MRIでは、個々の症例においてDTI解析の可否や、定量的な解析を実施し、データの蓄積を行っている。撮像データの解析、特にDTIデータの解析を目的として高機能のパーソナルコンピューターを別途購入し、専用のアプリケーションにて解析を実施した。 ラット脊髄損傷モデルに対して骨髄間葉系幹細胞(MSC)の経静脈投与することによって、中枢神経系にどのような神経回路の再構築(plasticity)が生じるかを検証するため、ラット胸髄Th9レベルの脊髄損傷モデルを作成し、動物用MRIでの撮像条件の最適化を検討した。8-9週齢のSDラットを購入し、ラット用脊髄損傷作 成装置(IH-0400 Impactor; PSI社製)を用いて、安定した損傷部位を作成できることを確認した。その後、動物実験用高磁場MRI装置にて、脳、脊髄おける各種プロトコール(T1、T2、DTI等)での撮像を行い、撮像条件の調整を行い最適な撮像条件の検討を行った。

• 実験的脳梗塞に対する骨髄幹細胞移植によって再構築される神経回路の網羅的解析

  基盤研究(C)

  研究期間:

  2021年04月

  -

  2024年03月

   

  長濱 宏史, 佐々木 祐典, 本望 修, 横山 貴裕, 鵜飼 亮

  　研究概要を見る

  我々は、これまでに実験的脳梗塞に対する骨髄間葉系幹細胞 (mesenchymal stem cells: MSCs)の経静脈的投与 (MSC治療)が、自然回復で得られる運動機能を凌駕する改善に貢献するメカニズムとして、脳の神経可塑性を賦活化することを明らかにしてきた。特に最近、 左右大脳皮質運動野における脳梁を介した神経線維連絡が損傷から保護されることをEx vivo MRI Diffusion Tensor Tractography (DTT) および、順行性神経軸索トレーサーによる神経解剖学的トレーシング法を用いた解析手法によって報告した。これらの成果から、我々は、実験的脳梗塞に対するMSC治療後の脳内には明らかな新規の神経回路の再構築が惹起されることを見出した。本研究では、実験的脳梗塞に対するMSC治療後の局所の神経線維連絡の再編にとどまらず、全脳の網羅的なコネクトーム解析を行い、神経線維ネットワークを最新のmagnetic resonance imaging (MRI)技術と神経解剖学的手法を用いて解析し、再構築される神経回路の全貌の解明を目指している。以上のように、補助金は適切に使用し、研究は予定通り進行中である。

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