Development of regenerative rehabilitation

• Project/Area Number: 18H03129
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: Kyoto University
• Principal Investigator: Kuroki Hiroshi 京都大学, 医学研究科, 教授 (20170110)
• Co-Investigator(Kenkyū-buntansha): 伊藤 明良 京都大学, 医学研究科, 講師 (50762134)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: リハビリテーション / 再生医学 / 理学療法 / 末梢神経 / 関節軟骨 / トレッドミル / 超音波刺激 / 免荷刺激 / 電気刺激 / 再生医療 / 移植医療

Outline of Final Research Achievements

From the viewpoint of basic research, the effects of ultrasonic intervention on peripheral nerve crush model of rats were mainly examined, and the effect was observed at an ultrasonic stimulation intensity of 60 mW/cm2. In addition, it is clear that ultrasound intervention for 1 week or 4 weeks from the next day of crush injury, not after 1 week after injury, promotes peripheral nerve regeneration, and that regulation of macrophage phenotype may be involved as one of the regeneration promoting mechanisms.

Academic Significance and Societal Importance of the Research Achievements

すでに生体臓器移植・組織移植が行われている中、細胞等を用いる再生医療が実施される新時代が訪れたことから、これら移植再生医療のリハビリテーションも重要となる。今回、末梢神経再生に関するリハビリテーション介入の一つである超音波介入の効果が検証されたこと、およびマクロファージ解析によって得られた成果をもとに今後そのメカニズムを解明する根拠が得られたことは学術的意義および社会的意義がある。

Research Products

• [Journal Article] Treadmill Exercise Suppresses Histological Progression of Disuse Atrophy in Articular Cartilage in Rat Knee Joints during Hindlimb Suspension (2023)
  • Author(s): Takahashi Ikufumi、Matsuzaki Taro、Kuroki Hiroshi、Hoso Masahiro
  • Journal Title: CARTILAGE Volume: 14 Issue: 4 Pages: 1-10
  • DOI: 10.1177/19476035231154510
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive Understanding of Inactivity-Induced Gait Alteration in Rodents (2022)
  • Author(s): Tajino Junichi、Aoyama Tomoki、Kuroki Hiroshi、Ito Akira
  • Journal Title: Journal of Visualized Experiments Volume: 185 Issue: 185
  • DOI: 10.3791/63865
  • Peer Reviewed
• [Journal Article] Ultrasound Therapy of Injury Site Modulates Gene and Protein Expressions in the Dorsal Root Ganglion in a Sciatic Nerve Crush Injury Rat Model (2022)
  • Author(s): Xu Shixuan、Ito Akira、Wang Tianshu、Kawai Hideki、Aoyama Tomoki、Kuroki Hiroshi
  • Journal Title: Ultrasound in Medicine & Biology Volume: 48 Issue: 12 Pages: 2502-2511
  • DOI: 10.1016/j.ultrasmedbio.2022.07.015
  • Peer Reviewed
• [Journal Article] Ultrasound Stimulation Inhibits Morphological Degeneration of Motor Endplates in the Denervated Skeletal Muscle of Rats (2022)
  • Author(s): Ito Akira、Araya Yuki、Kawai Hideki、Kuroki Hiroshi
  • Journal Title: Neuroscience Insights Volume: 17
  • DOI: 10.1177/26331055221138508
  • Peer Reviewed / Open Access
• [Journal Article] One session of 20 N cyclic compression induces chronic knee osteoarthritis in rats: A long-term study (2022)
  • Author(s): Zhao Zixi、Ito Akira、Nakahata Akihiro、Ji Xiang、Tai Chia、Saito Motoo、Nishitani Kohei、Aoyama Tomoki、Kuroki Hiroshi
  • Journal Title: Osteoarthritis and Cartilage Open Volume: 4 Issue: 4 Pages: 100325-100325
  • DOI: 10.1016/j.ocarto.2022.100325
  • Peer Reviewed / Open Access
• [Journal Article] Reduction of knee joint load suppresses cartilage degeneration, osteophyte formation, and synovitis in early-stage osteoarthritis using a post-traumatic rat model (2021)
  • Author(s): Takahashi I, Takeda K, Matsuzaki T, Kuroki H, Hoso M.
  • Journal Title: PLoS ONE Volume: 16 Issue: 7 Pages: e0254383-e0254383
  • DOI: 10.1371/journal.pone.0254383
  • Peer Reviewed / Open Access
• [Journal Article] Physiological reloading recovers histologically disuse atrophy of the articular cartilage and bone by hindlimb suspension in rat knee joint (2021)
  • Author(s): Takahashi I, Matsuzaki T, Kuroki H, Hoso M.
  • Journal Title: Cartilage Volume: 13 Issue: 2_suppl Pages: 1530S-1539S
  • DOI: 10.1177/19476035211063857
  • Peer Reviewed / Open Access
• [Journal Article] Correction to: Utilization of Mechanical Stress to Treat Osteoporosis: The Effects of Electrical Stimulation, Radial Extracorporeal Shock Wave, and Ultrasound on Experimental Osteoporosis in Ovariectomized Rats (2021)
  • Author(s): Inoue Shota、Hatakeyama Junpei、Aoki Hitoshi、Kuroki Hiroshi、Niikura Takahiro、Oe Keisuke、Fukui Tomoaki、Kuroda Ryosuke、Akisue Toshihiro、Moriyama Hideki
  • Journal Title: Calcified Tissue International Volume: 109 Issue: 2 Pages: 230-230
  • DOI: 10.1007/s00223-021-00867-8
  • Peer Reviewed
• [Journal Article] Intra-Articular Injections of Curcumin Monoglucuronide TBP1901 Suppresses Articular Cartilage Damage and Regulates Subchondral Bone Alteration in an Osteoarthritis Rat Model (2021)
  • Author(s): Nakahata Akihiro、Ito Akira、Nakahara Ryo、Kishimoto Atsuhiro、Imaizumi Atsushi、Hashimoto Tadashi、Mukai Shogo、Nakagawa Yasuaki、Kuroki Hiroshi
  • Journal Title: CARTILAGE Volume: 13 Issue: 2_suppl Pages: 153S-167S
  • DOI: 10.1177/19476035211043202
  • Peer Reviewed / Open Access
• [Journal Article] Utilization of Mechanical Stress to Treat Osteoporosis: The Effects of Electrical Stimulation, Radial Extracorporeal Shock Wave, and Ultrasound on Experimental Osteoporosis in Ovariectomized Rats (2021)
  • Author(s): Inoue S, Hatakeyama J, Aoki H, Kuroki H, Niikura T, Oe K, Fukui T, Kuroda R, Akisue T, Moriyama H.
  • Journal Title: Calcif Tissue Int. Volume: Epub Issue: 2 Pages: 215-229
  • DOI: 10.1007/s00223-021-00831-6
  • Peer Reviewed
• [Journal Article] Effects of ultrasound, radial extracorporeal shock waves, and electrical stimulation on rat bone defect healing (2021)
  • Author(s): Inoue S, Hatakeyama J, Aoki H, Kuroki H, Niikura T, Oe K, Fukui T, Kuroda R, Akisue T, Moriyama H.
  • Journal Title: Ann N Y Acad Sci. Volume: Epub Issue: 1 Pages: 3-14
  • DOI: 10.1111/nyas.14581
  • NAID: 120007126729
  • Peer Reviewed
• [Journal Article] Low-Intensity Pulsed Ultrasound Prompts Both Functional and Histologic Improvements While Upregulating the Brain-Derived Neurotrophic Factor Expression after Sciatic Crush Injury in Rats (2021)
  • Author(s): Wang T, Ito A, Xu S, Kawai H, Kuroki H, Aoyama T.
  • Journal Title: Ultrasound Med Biol. Volume: Epub Issue: 6 Pages: 1586-1595
  • DOI: 10.1016/j.ultrasmedbio.2021.02.009
  • NAID: 120007052719
  • Peer Reviewed
• [Journal Article] Disuse atrophy of articular cartilage induced by unloading condition accelerates histological progression of osteoarthritis in a post-traumatic rat model (2020)
  • Author(s): Takahashi I, Matsuzaki T, Kuroki H, Hoso M
  • Journal Title: Cartilage. Volume: - Issue: 2_suppl Pages: 1522S-1529S
  • DOI: 10.1177/1947603520982350
  • Peer Reviewed / Open Access
• [Journal Article] Quantitative Parameters for the Degeneration in Cartilage and Subchondral Bone of Human Knee by 3-D Ultrasound Scanning System (2020)
  • Author(s): Kiyan W, Nakagawa Y, Mukai S, Ito A, Arai T, Kuroki H.
  • Journal Title: Ultrasound Med Biol. Volume: 46 Issue: 12 Pages: 3239-3248
  • DOI: 10.1016/j.ultrasmedbio.2020.08.024
  • Peer Reviewed
• [Journal Article] Ultrasound therapy with optimal intensity facilitates peripheral nerve regeneration in rats through suppression of pro-inflammatory and nerve growth inhibitor gene expression (2020)
  • Author(s): Ito A, Wang T, Nakahara R, Kawai H, Nishitani K, Aoyama T, Kuroki H.
  • Journal Title: PLoS One Volume: 15 Issue: 6 Pages: e0234691-e0234691
  • DOI: 10.1371/journal.pone.0234691
  • NAID: 120006867161
  • Peer Reviewed / Open Access
• [Journal Article] 3D Kinematic Analysis for the Functional Evaluation in the Rat Model of Sciatic Nerve Crush Injury (2020)
  • Author(s): Wang T, Ito A, Tajino J, Kuroki H, Aoyama T
  • Journal Title: J. Vis. Exp Volume: 156 Issue: 156
  • DOI: 10.3791/60267
  • NAID: 120006870866
  • Peer Reviewed / Open Access
• [Journal Article] Taking the Next Steps in Regenerative Rehabilitation: Establishment of a New Interdisciplinary Field (2020)
  • Author(s): Willett NJ, Aoyama T, Ito A, Kuroki H, Tajino J, Ambrosio F, et al.
  • Journal Title: Arch Phys Med Rehabil Volume: 101 Issue: 5 Pages: 917-923
  • DOI: 10.1016/j.apmr.2020.01.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Therapeutic effects of combined cell transplantation and locomotor training in rats with brain injury. (2019)
  • Author(s): Shimogawa T, Sakaguchi H, Kikuchi T, Tsuchimochi R, Sano N, Torikoshi S, Ito A, Aoyama T, Iihara K, Takahashi J.
  • Journal Title: NPJ Regen Med. Volume: 4 Issue: 1 Pages: 13-13
  • DOI: 10.1038/s41536-019-0075-6
  • Peer Reviewed / Open Access
• [Journal Article] Three-dimensional motion analysis for evaluating motor function in rodents with peripheral nerve injury (2019)
  • Author(s): Ito Akira、Tianshu Wang、Tajino Junichi
  • Journal Title: Neural Regeneration Research Volume: 14 Issue: 12 Pages: 2077-2077
  • DOI: 10.4103/1673-5374.262581
  • NAID: 120006867157
  • Peer Reviewed / Open Access
• [Journal Article] Lower-body positive pressure diminishes surface blood flow reactivity during treadmill walking (2019)
  • Author(s): Tajino J, Ito A, Torii Y, Tsuchimoto K, Iijima H, Zhang X, Tanima M, Yamaguchi S, Ieki H, Kakinoki R, Kuroki H
  • Journal Title: BMC Res Notes Volume: 12 Issue: 1 Pages: 733-733
  • DOI: 10.1186/s13104-019-4766-2
  • Peer Reviewed / Open Access
• [Journal Article] Periodic mild heat stimuli diminish extracellular matrix synthesis in pellet cultured human chondrocytes. (2019)
  • Author(s): Ito A, Aoyama T, Iijima H, Nishitani K, Tajino J, Kuroki H.
  • Journal Title: BMC Res Notes Volume: 14 Issue: 1 Pages: 16-16
  • DOI: 10.1186/s13104-019-4058-x
  • NAID: 120006636640
  • Peer Reviewed
• [Journal Article] Functional evaluation outcomes correlate with histomorphometric changes in the rat sciatic nerve crush injury model: A comparison between sciatic functional index and kinematic analysis (2018)
  • Author(s): Wang Tianshu、Ito Akira、Aoyama Tomoki、Nakahara Ryo、Nakahata Akihiro、Ji Xiang、Zhang Jue、Kawai Hideki、Kuroki Hiroshi
  • Journal Title: PLOS ONE Volume: 13 Issue: 12 Pages: 1-9
  • DOI: 10.1371/journal.pone.0208985
  • NAID: 120006546016
  • Peer Reviewed / Open Access
• [Journal Article] Three-dimensional motion analysis for comprehensive understanding of gait characteristics after sciatic nerve lesion in rodents (2018)
  • Author(s): Tajino Junichi、Ito Akira、Tanima Momoko、Yamaguchi Shoki、Iijima Hirotaka、Nakahata Akihiro、Kiyan Wataru、Aoyama Tomoki、Kuroki Hiroshi
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 1-9
  • DOI: 10.1038/s41598-018-31579-z
  • NAID: 120006529728
  • Peer Reviewed / Open Access
• [Journal Article] Ultrasound Parameters for Human Osteoarthritic Subchondral Bone ex Vivo: Comparison with Micro-Computed Tomography Parameters. (2018)
  • Author(s): Kiyan W, Nakagawa Y, Ito A, Iijima H, Nishitani K, Tanima-Nagai M, Mukai S, Tajino J, Yamaguchi S, Nakahata A, Zhang J, Aoyama T, Kuroki H.
  • Journal Title: Ultrasound Med Biol Volume: 44 Issue: 10 Pages: 2115-2130
  • DOI: 10.1016/j.ultrasmedbio.2018.06.003
  • Peer Reviewed
• [Journal Article] Effectiveness of mesenchymal stem cells for treating patients with knee osteoarthritis: a meta-analysis toward the establishment of effective regenerative rehabilitation. (2018)
  • Author(s): Iijima H, Isho T, Kuroki H, Takahashi M, Aoyama T.
  • Journal Title: NPJ Regen Med Volume: 17 Issue: 1 Pages: 15-15
  • DOI: 10.1038/s41536-018-0041-8
  • Peer Reviewed
• [Presentation] ラット膝関節の術後癒着に対する超音波照射強度と時間の影響の検証 (2022)
  • Author(s): 中原崚，伊藤明良，谷間桃子，河合秀紀，趙梓汐，徐仕軒，戴嘉，安孫子幸子，青山朋樹，黒木裕士
  • Organizer: 第27回日本基礎理学療法学会学術大会
• [Presentation] 坐骨神経挫滅損傷モデルラットに対する超音波治療が脊髄後根神経節に与える影響の検討 (2022)
  • Author(s): 徐仕軒，伊藤明良，河合秀紀，中原崚，趙梓汐，戴嘉，青山朋樹，黒木裕士
  • Organizer: 第27回日本基礎理学療法学会学術大会
• [Presentation] 超音波パルス刺激は脱神経筋におけるアセチルコリン受容体の形態変性を抑制する (2022)
  • Author(s): 伊藤明良，河合秀紀，中原崚，徐仕軒，趙梓汐，戴嘉，黒木裕士
  • Organizer: 第27回日本基礎理学療法学会学術大会
• [Presentation] Ultrasound therapy for a week after injury accelerates the regeneration in a rat sciatic nerve autograft model (2022)
  • Author(s): Hideki Kawai, Akira Ito, Momoko Nagai-Tanima, Ryo Nakahara, Hiroshi Kuroki
  • Organizer: Ninth Annual International Symposium on Regenerative Rehabilitation
  • Int'l Joint Research
• [Presentation] Analysis of gene expression after ultrasound therapy for intraarticular adhesion model in rats (2022)
  • Author(s): Ryo Nakahara, Akira Ito, Momoko Nagai-Tanima, Hideki Kawai, Zixi Zhao, Chia Tai, Hiroshi Kuroki
  • Organizer: Ninth Annual International Symposium on Regenerative Rehabilitation
  • Int'l Joint Research
• [Presentation] Decelerating the process of articular cartilage degeneration in a non-invasive mechanical compression-induced rat model via intra-articular injections of allogeneic BMSCs (2022)
  • Author(s): Chia Tai, Akira Ito, Zixi Zhao, Ryo Nakahara, Hideki Kawai, Hiroshi Kuroki
  • Organizer: Ninth Annual International Symposium on Regenerative Rehabilitation
  • Int'l Joint Research
• [Presentation] The effect of ultrasound therapy on dorsal root ganglion in sciatic nerve crush injury rat model (2022)
  • Author(s): Shixuan Xu, Akira Ito, Hideki Kawai, Ryo Nakahara, Zixi Zhao, Chia Tai, Tomoki Aoyama, Hiroshi Kuroki
  • Organizer: Ninth Annual International Symposium on Regenerative Rehabilitation
  • Int'l Joint Research
• [Presentation] 坐骨神経挫滅損傷モデルラットに対する運動機能回復促進に最適な超音波照射開始時期の検証 (2020)
  • Author(s): 河合秀紀、伊藤明良、王天舒、中畑晶博、中原崚、徐仕軒、青山朋樹、黒木裕士
  • Organizer: 第25回日本基礎理学療法学会学術大会