Education 【 display / non-display 】

Education 【 display / non-display 】

• 2002

  -

  2006

  Sapporo Medical University   Graduate School of Medicine  

• 1995

  -

  2001

  Sapporo Medical University   医学部  

Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2023.04

  -

  Now

  Sapporo Medical University   Research Institute for Frontier Medicine   講師

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Neurosurgery  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   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  

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Intravenous Infusion of Autologous Mesenchymal Stem Cells Expanded in Auto Serum for Chronic Spinal Cord Injury Patients: A Case Series.

  Ryosuke Hirota, Masanori Sasaki, Satoshi Iyama, Kota Kurihara, Ryunosuke Fukushi, Hisashi Obara, Tsutomu Oshigiri, Tomonori Morita, Masahito Nakazaki, Takahiro Namioka, Ai Namioka, Rie Onodera, Yuko Kataoka-Sasaki, Shinichi Oka, Mitsuhiro Takemura, Ryo Ukai, Takahiro Yokoyama, Yuichi Sasaki, Tatsuro Yamashita, Masato Kobayashi, Yusuke Okuma, Reiko Kondo, Ryo Aichi, Satoko Ohmatsu, Noritaka Kawashima, Yoichi M Ito, Masayoshi Kobune, Kohichi Takada, Sumio Ishiai, Toru Ogata, Atsushi Teramoto, Toshihiko Yamashita, Jeffery D Kocsis, Osamu Honmou

  Journal of clinical medicine   13 ( 20 )  2024.10  [International journal]

  　View Summary

  Objective: The safety, feasibility, and potential functional improvement following the intravenous infusion of mesenchymal stem cells (MSCs) were investigated in patients with chronic severe spinal cord injury (SCI). Methods: The intravenous infusion of autologous MSCs cultured in auto-serum under Good Manufacturing Practices (GMP) was administered to seven patients with chronic SCI (ranging from 1.3 years to 27 years after the onset of SCI). In addition to evaluating feasibility and safety, neurological function was evaluated using the American Spinal Injury Association Impairment Scale (AIS), International Standards for Neurological Classification of Spinal Cord Injury (ISCSCI-92), and Spinal Cord Independence Measure III (SCIM-III). Results: No serious adverse events occurred. Neither CNS tumors, abnormal cell growth, nor neurological deterioration occurred in any patients. While this initial case series was not blinded, significant functional improvements and increased quality of life (QOL) were observed at 90 and 180 days post-MSC infusion compared to pre-infusion status. One patient who had an AIS grade C improved to grade D within six months after MSC infusion. Conclusions: This case series suggests that the intravenous infusion of autologous MSCs is a safe and feasible therapeutic approach for chronic SCI patients. Furthermore, our data showed significant functional improvements and better QOL after MSC infusion in patients with chronic SCI. A blind large-scale study will be necessary to fully evaluate this possibility.

  DOI PubMed

• Intravenous Infusion of Autologous Mesenchymal Stem Cells Expanded in Auto Serum for Chronic Spinal Cord Injury Patients: A Case Series

  Ryosuke Hirota, Masanori Sasaki, Satoshi Iyama, Kota Kurihara, Ryunosuke Fukushi, Hisashi Obara, Tsutomu Oshigiri, Tomonori Morita, Masahito Nakazaki, Takahiro Namioka, Ai Namioka, Rie Onodera, Yuko Kataoka-Sasaki, Shinichi Oka, Mitsuhiro Takemura, Ryo Ukai, Takahiro Yokoyama, Yuichi Sasaki, Tatsuro Yamashita, Masato Kobayashi, Yusuke Okuma, Reiko Kondo, Ryo Aichi, Satoko Ohmatsu, Noritaka Kawashima, Yoichi M. Ito, Masayoshi Kobune, Kohichi Takada, Sumio Ishiai, Toru Ogata, Atsushi Teramoto, Toshihiko Yamashita, Jeffery D. Kocsis, Osamu Honmou

  Journal of Clinical Medicine   13 ( 20 )  2024.10

  　View Summary

  Objective: The safety, feasibility, and potential functional improvement following the intravenous infusion of mesenchymal stem cells (MSCs) were investigated in patients with chronic severe spinal cord injury (SCI). Methods: The intravenous infusion of autologous MSCs cultured in auto-serum under Good Manufacturing Practices (GMP) was administered to seven patients with chronic SCI (ranging from 1.3 years to 27 years after the onset of SCI). In addition to evaluating feasibility and safety, neurological function was evaluated using the American Spinal Injury Association Impairment Scale (AIS), International Standards for Neurological Classification of Spinal Cord Injury (ISCSCI-92), and Spinal Cord Independence Measure III (SCIM-III). Results: No serious adverse events occurred. Neither CNS tumors, abnormal cell growth, nor neurological deterioration occurred in any patients. While this initial case series was not blinded, significant functional improvements and increased quality of life (QOL) were observed at 90 and 180 days post-MSC infusion compared to pre-infusion status. One patient who had an AIS grade C improved to grade D within six months after MSC infusion. Conclusions: This case series suggests that the intravenous infusion of autologous MSCs is a safe and feasible therapeutic approach for chronic SCI patients. Furthermore, our data showed significant functional improvements and better QOL after MSC infusion in patients with chronic SCI. A blind large-scale study will be necessary to fully evaluate this possibility.

  DOI

• 慢性期重症頭部外傷症例に対する自家骨髄MSC静脈投与

  岡 真一, 八巻 智洋, 佐々木 祐典, 佐々木 優子, 浪岡 隆洋, 浪岡 愛, 中崎 公仁, 竹村 光広, 鵜飼 亮, 横山 貴裕, 小瀧 勝, 岩立 康男, 小林 繁樹, 本望 修

  Journal of Japan Coma Society: JJCS ( (一社)日本意識障害学会 )  32 ( 1 ) 103 - 103  2024.07

• Intravenous infusion of auto-serum-expanded autologous mesenchymal stem cells into chronic severe brain injury patients

  Tomohiro Yamaki, Shinichi Oka, Satoshi Iyama, Masanori Sasaki, Rie Onodera, Yuko Kataoka-Sasaki, Takahiro Namioka, Ai Namioka, Masahito Nakazaki, Mitsuhiro Takemura, Ryo Ukai, Takahiro Yokoyama, Yuichi Sasaki, Tatsuro Yamashita, Masato Kobayashi, Misako Yamaguchi, Marina Fukino, Taro Takazawa, Megumi Hayasaka, Takamitsu Owaku, Mika Funakura, Shinji Onodera, Yoichi M. Ito, Masayoshi Kobune, Junji Kato, Sumio Ishiai, Jeffery D. Kocsis, Masaru Odaki, Yasuo Iwadate, Shigeki Kobayashi, Osamu Honmou

  Interdisciplinary Neurosurgery ( Elsevier BV )  36   101927 - 101927  2024.06

  DOI

• Rehabilitation facilitates functional improvement following intravenous infusion of mesenchymal stem cells in the chronic phase of cerebral ischemia in rats.

  Tatsuro Yamashita, Masanori Sasaki, Yuichi Sasaki, Hiroshi Nagahama, Shinichi Oka, Yuko Kataoka-Sasaki, Ryo Ukai, Takahiro Yokoyama, Masato Kobayashi, Masafumi Kakizawa, Jeffery D Kocsis, Osamu Honmou

  Brain research   1825   148709 - 148709  2024.02  [International journal]

  　View Summary

  The primary objective of this study was to investigate the potential facilitating effects of daily rehabilitation for chronic cerebral ischemia following the intravenous infusion of mesenchymal stem cells (MSC) in rats. The middle cerebral artery (MCA) was occluded by intraluminal occlusion using a microfilament (MCAO). Eight weeks after MCAO induction, the rats were used as a chronic cerebral ischemia model. Four experimental groups were studied: Vehicle group (medium only, no cells); Rehab group (vehicle + rehabilitation), MSC group (MSC only); and Combined group (MSC + rehabilitation). Rat MSCs were intravenously infused eight weeks after MCAO induction, and the rats received daily rehabilitation through treadmill exercise for 20 min. Behavioral testing, lesion volume assessment using magnetic resonance imaging (MRI), and histological analysis were performed during the observation period until 16 weeks after MCAO induction. All treated animals showed functional improvement compared with the Vehicle group; however, the therapeutic efficacy was greatest in the Combined group. The combination therapy is associated with enhanced neural plasticity shown with histological analysis and MRI diffusion tensor imaging. These findings provide behavioral evidence for enhanced recovery by combined therapy with rehabilitation and intravenous infusion of MSCs, and may form the basis for the development of clinical protocols in the future.

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• Neurogenesisと神経再生医療 脳梗塞に対する骨髄幹細胞移植による脳循環の改善

  本望 修, 鵜飼 亮, 原田 邦明, 宝金 清博

  脳循環代謝 ( (一社)日本脳循環代謝学会 )  18 ( 4 ) 189 - 191  2006.12

  　View Summary

  脳梗塞モデルラットに対し、骨髄間葉系幹細胞(MSC)を経静脈的に投与すると、梗塞巣の縮小化や神経機能の改善が認められることが知られているが、脳血流に関する詳細な検討は報告されていない。今回、我々は、脳梗塞後1週間にわたり、脳梗塞周囲の組織の血流を解析し、治療機序の解明を試みた。ラット脳梗塞モデルは中大脳動脈永久閉塞モデルを用いた。経時的に高磁場(7T)MRIを用いて、DWI、T2WI、PWI(rCBV)を撮影し、脳血流と組織ダメージとの関連性を経時的に解析した。また、MSC移植群との比較解析を行い、治療効果を検討した。結果は、ischemic coreの脳血流は、極期においてもゼロにはならず、早期より改善傾向を呈したことより、細胞治療時の細胞デリバリールートとして体循環を利用する戦略が期待された。また、MSC移植治療により脳血流が著明に改善したことより、作用機序の一つに血管新生が関係していると思われた。(著者抄録)

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 慢性期脳梗塞に対する骨髄幹細胞治療における至適リハビリ条件の探索

  基盤研究(C)

  Project Year :

  2024.04

  -

  2027.03

   

  山下 達郎, 佐々木 雄一, 佐々木 祐典, 鵜飼 亮, 岡 真一, 佐々木 優子, 本望 修, 中崎 公仁

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

  基盤研究(C)

  Project Year :

  2024.04

  -

  2027.03

   

  岡 真一, 鵜飼 亮, 横山 貴裕, 中崎 公仁

• Therapeutic strategies for cerebral infarction and spinal cord injury by activating plasticity throughout the central nervous system

  Grant-in-Aid for Scientific Research (B)

  Project Year :

  2024.04

  -

  2025.03

   

  本望 修, 佐々木 雄一, 福士 龍之介, 佐々木 祐典, 小原 尚, 鵜飼 亮, 小林 萬里, 山下 達郎, 横山 貴裕, 岡 真一, 佐々木 優子, 中崎 公仁

• 脊髄損傷に対する骨髄幹細胞による治療メカニズムに占めるミトコンドリア機能の解析

  基盤研究(C)

  Project Year :

  2023.04

  -

  2026.03

   

  佐々木 祐典, 鵜飼 亮, 岡 真一, 佐々木 優子, 本望 修

  　View Summary

  脊髄損傷後に神経症状の増悪をもたらす二次損傷の病態解明は重要である。近年、二次損傷に占めるミトコンドリアの役割に注目が集まっており、脊髄損傷後に生じるミトコンドリアの機能不全によるATP合成不全が惹起するエネルギー代謝不全、活性酸素の産生増加、神経毒性の増加などが神経症状の増悪に関与すると報告されている。一方、我々はこれまで、脊髄損傷ラットモデルおよび脊髄損傷患者に対する骨髄幹細胞の経静脈的投与 (MSC治療)による運動機能の改善を報告してきた。 この中で、MSC治療後に、ミトコンドリアの代謝機能に関連する遺伝子群が存在することを見出した。本研究では、脊髄損傷に対しMSC治療を実施し、①損傷局所および②大脳皮質の神経系細胞内におけるミトコンドリアの機能の変化を詳細に解析することを計画した。これらの解析を通じて、MSC治療により惹起される神経機能の回復に貢献するメカニズムにミトコンドリアが強く関与していることを明らかにし、次世代の治療法の開発に展開することを最終的な目標として、これまでに雄性SDラット (250-300g)に実験的脊髄損傷 (IH-0400 Impactor)を作製後にMSCの経静脈的投与を行い (MSC群)、運動機能を評価した。さらに、細胞外フラックスアナライザー (Xfe96, Agilent)を用いて、ミトコンドリアエネルギー代謝機能である酸素消費速度 (oxygen consumption rate: OCR)および細胞外酸性化速度(extracellular acidification rate: ECAR)を測定の予備的実験を開始した。

• Development of innovative treatments using next-generation exosomes for cerebral infarction

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2022.04

  -

  2025.03

   

  鵜飼 亮, 佐々木 祐典, 本望 修

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