Development of regenerative rehabilitation as the fourth element of regenerative medicine

• Project/Area Number: 26282154
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Rehabilitation science/Welfare engineering
• Research Institution: Kyoto University
• Principal Investigator: Aoyama Tomoki 京都大学, 医学(系)研究科(研究院), 准教授 (90378886)
• Co-Investigator(Kenkyū-buntansha): 黒木 裕士 京都大学, 医学(系)研究科(研究院), 教授 (20170110)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000); Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
• Keywords: 再生医療 / リハビリテーション / 関節軟骨再生 / エクササイズ / 物理療法 / 再生リハビリテーション

Outline of Final Research Achievements

Cell, scaffold, and nutrition are the three essential elements of regenerative medicine. However, these elements focus only on cells or tissues, but not organs and individuals. The purpose of this study was to develop and show the usefulness of rehabilitation resource to promote the regenerative effect of regenerative medicine. The osteochondral defect on rat knee joint was additively regenerated by mesenchymal stromal cell transplantation when combined with exercise or low-intensity pulsed ultrasonographic stimulation. These data suggest that rehabilitation programs can be the fourth element to promote the effect of regenerative medicine.

Research Products

• [Journal Article] Physiological exercise loading suppresses post-traumatic osteoarthritis progression via an increase in bone morphogenetic proteins expression in an experimental rat knee model (2017)
  • Author(s): Iijima H, Ito A, Nagai M, Tajino J, Yamaguchi S, Kiyan W, Nakahata A, Zhang J, Wang T, Aoyama T, Nishitani K, Kuroki H
  • Journal Title: Osteoarthritis and Cartilage Volume: 印刷中 Issue: 6 Pages: 964-975
  • DOI: 10.1016/j.joca.2016.12.008
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model. (2017)
  • Author(s): Yurie H, Ikeguchi R, Aoyama T, Kaizawa Y, Tajino J, Ito A, Ohta S, Oda H, Takeuchi H, Akieda S, Tsuji M, Nakayama K, Matsuda S.
  • Journal Title: PLoS One. Volume: 12 Issue: 2 Pages: 0171448-0171464
  • DOI: 10.1371/journal.pone.0171448
  • NAID: 120005980856
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A clinical trial for Kienbock disease by cultured autologous multipotent mesenchymal stromal cells augmented with vascularized bone grafts: A report of five cases. (2017)
  • Author(s): Ikeguchi R, Aoyama T, Kakinoki R, Ueda M, Kasai Y, Maekawa T, Tada H, Yamamoto M, Matsuda S, Nakamura T, Toguchida J.
  • Journal Title: J Orthop Sci. Volume: 17 Issue: 4 Pages: 30032-30035
  • DOI: 10.1016/j.jos.2017.02.002
  • Peer Reviewed / Open Access
• [Journal Article] 骨軟骨再生治療 (2017)
  • Author(s): 南角学、伊藤明良、黒田隆、青山朋樹．
  • Journal Title: 総合リハビリテーション Volume: 45 Pages: 13-9
  • Peer Reviewed
• [Journal Article] Remobilization causes site-specific cyst formation in immobilization-induced knee cartilage degeneration in an immobilized rat model. (2016)
  • Author(s): Nagai M, Ito A, Tajino J, Iijima H, Yamaguchi S, Zhang X, Aoyama T, Kuroki H.
  • Journal Title: Journal of Anatomy Volume: 印刷中 Issue: 6 Pages: 929-939
  • DOI: 10.1111/joa.12453
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Effect of Exercise on the Early Stages of Mesenchymal Stromal Cell-Induced Cartilage Repair in a Rat Osteochondral Defect Model (2016)
  • Author(s): Yamaguchi S, Aoyama T, Ito A, Nagai M, Iijima H, Tajino J, Zhang X, Kiyan W, Kuroki H
  • Journal Title: PLoS One Volume: 11 Issue: 3 Pages: 1-16
  • DOI: 10.1371/journal.pone.0151580
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of low-intensity pulsed ultrasound after mesenchymal stromal cell injection to treat osteochondral defects: An In Vivo study. (2016)
  • Author(s): Yamaguchi S, Aoyama T, Ito A, Nagai M, Iijima H, Tajino J, Zhang X, Wataru K, Kuroki H.
  • Journal Title: Ultrasound Med Biol. Volume: 42 Issue: 12 Pages: 2903-2913
  • DOI: 10.1016/j.ultrasmedbio.2016.07.021
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Rehabilitation program after cell therapy for treatment of femoral head osteonecrosis: A narrative review of literature. (2016)
  • Author(s): Aoyama T.
  • Journal Title: Int J Phys Med Rehabil. Volume: 4 Issue: 4 Pages: 354-354
  • DOI: 10.4172/2329-9096.1000354
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A strategy of bone regeneration for the treatment of idiopathic femoral head necrosis. Advanced techniques in bone regeneration. (2016)
  • Author(s): Aoyama T.
  • Journal Title: InTech. Volume: 1 Pages: 91-106
  • DOI: 10.5772/62478
  • ISBN: 9789535125389, 9789535125396
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Plasma microRNAs Are Potential Biomarkers of Acute Rejection After Hindlimb Transplantation in Rats. (2016)
  • Author(s): Oda H, Ikeguchi R, Yurie H, Kaizawa Y, Ohta S, Yamamoto K, Aoyama T, Matsuda S.
  • Journal Title: Transplant Direct. Volume: 2 Issue: 11 Pages: e108-e108
  • DOI: 10.1097/txd.0000000000000620
  • Peer Reviewed
• [Journal Article] 先端医療と理学療法． (2016)
  • Author(s): 南角学、青山朋樹、黒田隆．
  • Journal Title: 理学療法ジャーナル. Volume: 50 Pages: 77-9
  • Peer Reviewed
• [Journal Article] Rehabilitation program after mesenchymal stromal cell transplantation augmented by vascularized bone grafts for idiopathic osteonecrosis of the femoral head: A preliminary study. (2015)
  • Author(s): Aoyama T, Fujita Y, Madoba K, Nankaku M, Yamada M, Tomita M, Goto K, Ikeguchi R, Kakinoki R, Matsuda S, Nakamura T, Toguchida J.
  • Journal Title: Arch Phys Med Rehabil Volume: 96 Issue: 3 Pages: 532-9
  • DOI: 10.1016/j.apmr.2014.09.040
  • NAID: 120005575166
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Culture temperature affects human chondrocyte messenger RNA expression in monolayer and pellet culture systems (2015)
  • Author(s): Ito A, Nagai M, Tajino J, Yamaguchi S, Iijima H, Zhang X, Aoyama T, Kuroki H
  • Journal Title: PLoS One Volume: 26 Issue: 5 Pages: e0128082-e0128082
  • DOI: 10.1371/journal.pone.0128082
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Culture temperature affects redifferentiation and cartilaginous extracellular matrix formation in dedifferentiated human chondrocytes (2015)
  • Author(s): Ito A, Aoyama T, Iijima H, Tajino J, Nagai M, Yamaguchi S, Zhang X, Kuroki H
  • Journal Title: J Orthop Res Volume: なし Issue: 5 Pages: 633-9
  • DOI: 10.1002/jor.22808
  • Peer Reviewed
• [Journal Article] Effect of microfabricated microgroove-surface devices on the morphology of mesenchymal stem cells. (2015)
  • Author(s): Zhang X, Aoyama T, Yasuda T, Oike M, Ito A, Tajino J, Nagai M, Fujioka R, Iijima H, Yamaguchi S, Kakinuma N, Kuroki H.
  • Journal Title: Biomed Microdevices Volume: 17 Pages: 116-116
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Regional comparisons of porcine menisci. (2014)
  • Author(s): Zhang X, Aoyama T, Ito A, Tajino J, Nagai M, Yamaguchi S, Iijima H, Kuroki H.
  • Journal Title: J Orthop Res Volume: 32 Pages: 1602-11
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Destabilization of the medial meniscus leads to subchondral bone defects and site-specific cartilage degeneration in an experimental rat model. (2014)
  • Author(s): Iijima H, Aoyama T, Ito A, Tajino J, Nagai M, Zhang X, Yamaguchi S, Akiyama H, Kuroki H.
  • Journal Title: Osteoarthritis Cartilage Volume: 22 Pages: 1036-43
  • Peer Reviewed
• [Journal Article] Three-dimensional reconstruction of rat knee joint using episcopic fluorescence image capture. (2014)
  • Author(s): Takaishi R, Aoyama T, Zhang X, Higuchi S, Yamada S, Takakuwa T.
  • Journal Title: Osteoarthritis Cartilage. Volume: 22 Pages: 1401-9
  • NAID: 120005512272
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Peripheral Nerve Regeneration Using Bio 3D Conduit. (2017)
  • Author(s): Hirofumi Yurie, Ryosuke Ikeguchi, Tomoki Aoyama, Yukitoshi Kaizawa, Junichi Tajino, Akira Ito, Souichi Ohta, Hiroki Oda, Takahisa Takeuchi1, Shizuka Akieda, Manami Tsuji, Koichi Nakayama, Shuichi Matsuda.
  • Organizer: ORS 2017 Annual Meeting.
  • Place of Presentation: San Diego, California
  • Year and Date: 2017-03-19
  • Int'l Joint Research
• [Presentation] Elevated Plasma MicroRNA-155, As A Biomarker Of Hind Limb Transplant Rejection In Rats. (2017)
  • Author(s): Hiroki Oda, Ryosuke Ikeguchi, Tomoki Aoyama, Hisataka Takeuchi, Hirofumi Yurie, Yukitoshi Kaizawa, Souichi Ohta, Koji Yamamoto, Shuichi Matsuda.
  • Organizer: ORS 2017 Annual Meeting.
  • Place of Presentation: San Diego, California
  • Year and Date: 2017-03-19
  • Int'l Joint Research
• [Presentation] ラット坐骨神経欠損モデルにおけるBio 3D conduitの有用性の検討． (2017)
  • Author(s): 淘江宏文、池口良輔、青山朋樹、太治野純一、貝澤幸俊、太田壮一、織田宏基、竹内久貴、秋枝静香、辻真奈美、中山功一、松田秀一．
  • Organizer: 第16回日本再生医療学会総会．
  • Place of Presentation: 仙台市
  • Year and Date: 2017-03-07
• [Presentation] 大腿骨頭壊死症に対する細胞治療におけるリハビリテーションのフィージビリティ調査． (2017)
  • Author(s): 青山朋樹、池口良輔、松田秀一．
  • Organizer: 第16回日本再生医療学会総会．
  • Place of Presentation: 仙台市
  • Year and Date: 2017-03-07
• [Presentation] キーンベック病に対する骨髄間葉系幹細胞を用いた細胞治療について． (2017)
  • Author(s): 池口良輔、青山朋樹、柿木良介、上田路子、笠井泰成、前川平、多田春江、山本倫生、松田秀一、中村孝志、戸口田淳也．
  • Organizer: 第16回日本再生医療学会総会．
  • Place of Presentation: 仙台市
  • Year and Date: 2017-03-07
• [Presentation] Bio 3D printingを用いた人工神経による末梢神経再生． (2016)
  • Author(s): 淘江宏文、池口良輔、青山朋樹、貝澤幸俊、太治野純一、伊藤明良、張項凱、太田壮一、織田宏基、秋枝静香、辻真奈美、中山功一、松田秀一．
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 2016-10-13
• [Presentation] ラット四肢移植モデルにおける血漿中micro RNAの検討． (2016)
  • Author(s): 織田宏基、池口良輔、淘江宏文、貝澤幸俊、太田壮一、山本浩司、青山朋樹、松田秀一．
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 2016-10-13
• [Presentation] Plasma micro RNA-155 is a potential biomaker if acute rejection after hind limb transplantation in rats. (2016)
  • Author(s): Hiroki Oda, Ryosuke Ikeguchi, Akira Ito, Hirofumi Yurie, Yukitoshi Kaizawa, Souichi Ohta, Koji Yamamoto, Tomoki Aoyama, Shuichi Matsuda.
  • Organizer: XXI Congress of Federation of European Society for Surgery of the Hand
  • Place of Presentation: Santander, Spain.
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Presentation] Peripheral nerve regeneration using Bio 3D conduit. (2016)
  • Author(s): Hirofumi Yurie, Ryosuke Ikeguchi, Tomoki Aoyama, Yukitoshi Kaizawa, Souichi Ohta, Hiroki Oda, Junichi Tajino, Zhang Xiangkai, Shizuka Akieda, Manami Tsuji, Koichi Nakayama, Shuichi Matsuda.
  • Organizer: XXI Congress of Federation of European Society for Surgery of the Hand
  • Place of Presentation: Santander, Spain.
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Presentation] Feasibility study of rehabilitation program after mesenchymal stromal cell transplantation for idiopathic osteonecrosis of the femoral head. (2015)
  • Author(s): Tomoki Aoyama.
  • Organizer: Fourth Annual symposium on Regenerative rehabilitation.
  • Place of Presentation: Rochester, MN.
  • Year and Date: 2015-09-24
  • Int'l Joint Research
• [Presentation] Periodic heat stimulus for extracellular matrix production on human chondrocytes. (2015)
  • Author(s): A. Ito, H. Iijima, J. Tajino, M. Nagai, S. Yamaguchi, X. Zhang, T. Aoyama, H. Kuroki.
  • Organizer: Fourth Annual symposium on Regenerative rehabilitation.
  • Place of Presentation: Rochester, MN.
  • Year and Date: 2015-09-24
  • Int'l Joint Research
• [Presentation] Efficacy of LIPUS treatment following mesenchymal stromal cell intra-articular injection in an osteochondral defect model rats. (2015)
  • Author(s): S. Yamaguchi, T. Aoyama, A. Ito, M. Nagai, H. Iijima, J. Tajino, X. Zhang, W.Kiyan, H. Kuroki.
  • Organizer: Fourth Annual Symposium on Regenerative Rehabilitation
  • Place of Presentation: Rochester, MN.
  • Year and Date: 2015-09-24
  • Int'l Joint Research
• [Presentation] The effect of low intensity pulsed ultrasound treatment combined with mesenchymal stromal cell injection for cartilage regeneration in a knee osteochondral defect model of rats. (2015)
  • Author(s): S. Yamaguchi, T. Aoyama, A. Ito, M. Nagai, H. Iijima, J. Tajino, X. Zhang, W.Kiyan, H. Kuroki.
  • Organizer: 2015 World Congress on Osteoarthritis
  • Place of Presentation: Seattle, WA
  • Year and Date: 2015-04-30
  • Int'l Joint Research
• [Presentation] Effect of initiation timing of gentle treadmill exercise on cartilage and subchondral bone in a model of destabilization of medial meniscus of rats. (2015)
  • Author(s): H. Iijima, T. Aoyama, A. Ito, S. Yamaguchi, M. Nagai, J. Tajino, X. Zhang, W. Kiyan, H. Kuroki.
  • Organizer: 2015 World Congress on Osteoarthritis
  • Place of Presentation: Seattle, WA
  • Year and Date: 2015-04-30
  • Int'l Joint Research
• [Presentation] Effects of culturing temperature on extracellular matrix formation and redifferentiation of expanded human chondrocyte. (2014)
  • Author(s): A. Ito, T. Aoyama, J. Tajino, M. Nagai, S. Yamaguchi, H. Iijima, X. Zhang, H. Akiyama, H. Kuroki.
  • Organizer: 2014 World Congress on Osteoarthritis
  • Place of Presentation: Paris
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] Regional changes of early osteoarthritis cartilage and subchondral bone fracture in a rat knee model of OA. (2014)
  • Author(s): H. Iijima, T. Aoyama, A. Ito, S. Yamaguchi, M. Nagai, J. Tajino, X. Zhang, H. Akiyama, H. Kuroki
  • Organizer: 2014 World Congress on Osteoarthritis
  • Place of Presentation: Paris
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] Mild thermal environment enhances redifferentiation and cartilage extracellular matrix formation of expanded elderly human chondrocytes. (2014)
  • Author(s): A. Ito, S. Yamaguchi, J. Tajino, M. Nagai, H. Iijima, X. Zhang, T. Aoyama, H. Kuroki.
  • Organizer: Third Annual Symposium on Regenerative Rehabilitation
  • Place of Presentation: San Francisco
  • Year and Date: 2014-04-10 – 2014-04-11
• [Presentation] Efficacy of exercise following bone marrow mesenchymal stromal cell transplantation in an osteochondral defect model of rats. (2014)
  • Author(s): S. Yamaguchi, T. Aoyama, A. Ito, M. Nagai, H. Iijima, J. Tajino, X. Zhang, H. Akiyama, H. Kuroki
  • Organizer: Third Annual Symposium on Regenerative Rehabilitation
  • Place of Presentation: San Francisco
  • Year and Date: 2014-04-10 – 2014-04-11
• [Presentation] Cartilage degeneration in immobilization rat knee joint deteriorated with re-mobilization (2014)
  • Author(s): M. Nagai, T. Aoyama, A. Ito, J. Tajino, S. Yamaguchi, H. Iijima, X. Zhang, H. Akiyama, H. Kuroki
  • Organizer: Third Annual Symposium on Regenerative Rehabilitation
  • Place of Presentation: San Francisco
  • Year and Date: 2014-04-10 – 2014-04-11
• [Book] 再生医療のための細胞製造ハンドブック (2015)
  • Author(s): 青山朋樹、仙石慎太郎
  • Total Pages: 196
  • Publisher: シーエムシー出版.
• [Book] リハビリテーション現場における超音波検査の実践 (2014)
  • Author(s): 青山朋樹
  • Total Pages: 82
  • Publisher: 全日本病院出版
• [Remarks] 再生リハビリテーション
  • URL: http://regenerative-rehabilitation.com/jp/
• [Remarks] Humanalysis Square
  • URL: http://www.humanalysis-square.com/
• [Remarks] Regenerative Rehabilitation
  • URL: http://regenerative-rehabilitation.com/
• [Funded Workshop] 第三回国際再生リハビリテーションシンポジウム (2017)
  • Place of Presentation: 京都
• [Funded Workshop] 2nd International Symposium on Regenerative Rehabilitation in Kyoto. (2016)
  • Place of Presentation: Kyoto
  • Year and Date: 2016-03-25