Akira Ito, Ph.D., PT
Department of Physical Therapy, Human Health Sciences,
Graduate School of Medicine, Kyoto University
A. Personal Statement
Several years ago, I worked as a physical therapist at a hospital and gained valuable experience treating patients with a variety of pathologies including osteoarthritis and peripheral nerve injuries. More recently, as a graduate student and a postdoctoral fellow at Kyoto University in Japan, I studied molecular and cellular biology, animal experimentation, and various analytical methods. These studies led to several peer-reviewed publications on which I was the principal investigator. From these experiences, I have gained sufficient knowledge in the fields of rehabilitation and cellular biology that formed the foundation for my current research focus in the field of Regenerative Rehabilitation. My long-term research interests involve the elucidation of the effects and underlying mechanisms of physical therapy for regenerative medicine. Ultimately, I am interested in clinically translating these findings into the development of more effective physical therapies. I am fortunate to have experienced collaborators who specialize in hand and peripheral nerve surgery, rehabilitation, regenerative medicine, and 3D bioprinting. My clinical and research experiences in rehabilitation and regenerative medicine, strong team of collaborators, and strong motivation render me well poised to successfully carry out my proposed work in the area of regenerative rehabilitation.
1. Ito A, Aoyama T, Iijima H, Tajino J, Nagai M, Yamaguchi S, Zhang X, Kuroki H. Culture temperature affects redifferentiation and cartilaginous extracellular matrix formation in dedifferentiated human chondrocytes. J Orthop Res. 2015 May;33(5):633-9. PubMed PMID: 25641400.
2. Ito A, Aoyama T, Yoshizawa M, Nagai M, Tajino J, Yamaguchi S, Iijima H, Zhang X, Kuroki H. The effects of short-term hypoxia on human mesenchymal stem cell proliferation, viability and p16(INK4A) mRNA expression: Investigation using a simple hypoxic culture system with a deoxidizing agent. J Stem Cells Regen Med. 2015;11(1):25-31. PubMed PMID: 26195892; PubMed Central PMCID: PMC4498321.
3. Ito A, Nagai M, Tajino J, Yamaguchi S, Iijima H, Zhang X, Aoyama T, Kuroki H. Culture temperature affects human chondrocyte messenger RNA expression in monolayer and pellet culture systems. PLoS One. 2015;10(5):e0128082. PubMed PMID: 26010859; PubMed Central PMCID: PMC4444092.
4. Ito A, Aoyama T, Yamaguchi S, Zhang X, Akiyama H, Kuroki H. Low-intensity pulsed ultrasound inhibits messenger RNA expression of matrix metalloproteinase-13 induced by interleukin-1β in chondrocytes in aAssistant Professor of Physical Therapy, Kyoto University, Kyoto, Japann intensity-dependent manner. Ultrasound Med Biol. 2012 Oct;38(10):1726-33. PubMed PMID: 22920551.
Complete List of Published Work in My Bibliography:
Dates/Attended Name, Location of Institution/Degree Received/Year
2012-2015/Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan/Ph.D. of Human Health Sciences/2015
2010-2012/Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan/Master of Human Health Sciences/2012
2008-2010/Faculty of Medicine, Human Health Sciences, Kyoto University, Kyoto city, Japan/Bachelor of Human Health Sciences/2010
2000-2003/Rehabilitation Gakuin attached to the National Hospital Organization Higashi Nagoya National Hospital, Nagoya city, Japan/Physical Therapist/2003
C. Positions and Honors
Positions and Employment
2003 - 2008 Physical Therapist, Wada Hospital, Nagoya
2013 - 2015 Research Fellow of Japan Society for the Promotion of Science (DC2), Kyoto University, Kyoto
2015 - 2015 Part-time Lecturer, Kyoto University, Kyoto
2015 - 2016 Research Fellow of Japan Society for the Promotion of Science (PD), Kyoto University, Kyoto
2016 - Assistant Professor of Physical Therapy, Kyoto University, Kyoto
Other Experience and Professional Memberships
2003 - Member, The Japanese Physical Therapy Association
2010 - Member, Japanese Society of Developmental Biologists
2011 - Member, Osteoarthritis Research Society International
2011 - Member, The Japanese Society of Cartilage Metabolism
2015 - Member, the Japanese Bio-Electrical and Physical Stimulation Research Society
2016 - Asia-Pacific Group Member, Tissue Engineering International & Regenerative Medicine Society (termis), Regenerative Rehabilitation Group
2012 Best Master’s course Student Award, Human Health Sciences, Graduate School of Medicine, Kyoto University
2013 Best Paper Award , The Japanese Physical Therapy Association
2013 Encouragement Award of the 47th Congress of the Japanese Physical Therapy Association, The Japanese Physical Therapy Association
2014 Travel Scholarship, Japan foundation for Aging and Health
2016 Grant of Study Abroad, The Nakatomi Foundation
D. Contribution to Science
1. My early publications addressed the regulation of inflammatory responses in articular cartilage using low-intensity pulsed ultrasound (LIPUS). Osteoarthritis (OA) is a highly prevalent degenerative disease characterized by progressive joint destruction. Although many approaches to the treatment of various aspects of OA have been studied, the need remains for more effective treatments. Mechanical stimuli are recognized as critical factors in regulating chondrocyte metabolism. In particular, physiological mechanical stimuli have been shown to promote chondrocyte anabolism and suppress chondrocyte catabolism. In this regard, LIPUS is a promising approach to induce micromechanical stress in targeted sites. While the effects of LIPUS on anabolic processes in articular cartilage have been studied, the effects of LIPUS on catabolic processes in articular cartilage remain unknown. Therefore, we investigated the intensity-dependent acute effects of LIPUS on chondrocytes treated with inflammatory stimulus IL-1β. From this work, we demonstrated that LIPUS inhibits inflammation induced matrix metallopeptidase 13 (MMP13) mRNA expression in an intensity-dependent manner. This study, on which I served as the principal investigator, were the first to demonstrate that LIPUS treatment shows potential as a therapeutic approach for OA by specifically suppressing processes.
a. Ito A, Aoyama T, Yamaguchi S, Zhang X, Akiyama H, Kuroki H. Low-intensity pulsed ultrasound inhibits messenger RNA expression of matrix metalloproteinase-13 induced by interleukin-1β in chondrocytes in an intensity-dependent manner. Ultrasound Med Biol. 2012 Oct;38(10):1726-33. PubMed PMID: 22920551.
2. Ambient temperatures markedly influence human body temperature. However, few studies have investigated the influence of temperature on the repair of living body tissues, namely skeletal muscle and articular cartilage. We deliberated why regenerative therapies (e.g., utilizing implanted cells or regenerative therapeutics) were not entirely effective at such a low-temperature environment and hypothesized that tissue regeneration could be promoted through appropriate regulation of tissue temperature. In order to elucidate the effect of thermal environment, we investigated the effects of culture temperature on re-differentiation and cartilaginous extracellular matrix (ECM) formation in de-differentiated human chondrocytes. These studies demonstrated that the physiologic temperature of 37°C was superior in promoting chondrocyte re-differentiation and cartilaginous ECM formation compared to a decreased temperature of 32°C, which mimics in vivo intra-articular temperature. Furthermore, elevated temperatures of 41°C drastically inhibited cartilaginous ECM formation. Therefore, thermo-regulation is a key factor in regulating the phenotype and biosynthetic activity of chondrocytes. I served as the primary investigator in this work.
a. Ito A, Aoyama T, Iijima H, Tajino J, Nagai M, Yamaguchi S, Zhang X, Kuroki H. Culture temperature affects redifferentiation and cartilaginous extracellular matrix formation in dedifferentiated human chondrocytes. J Orthop Res. 2015 May;33(5):633-9. PubMed PMID: 25641400.
b. Ito A, Nagai M, Tajino J, Yamaguchi S, Iijima H, Zhang X, Aoyama T, Kuroki H. Culture temperature affects human chondrocyte messenger RNA expression in monolayer and pellet culture systems. PLoS One. 2015;10(5):e0128082. PubMed PMID: 26010859; PubMed Central PMCID: PMC4444092.
c. Ito A, Aoyama T, Tajino J, Nagai M, Yamaguchi S, Iijima H, Zhang X, Akiyama H, Kuroki H. Evaluation of reference genes for human chondrocytes cultured in several different thermal environments. Int J Hyperthermia. 2014 May;30(3):210-6. PubMed PMID: 24773042.
d. Ito A, Aoyama T, Iijima H, Nagai M, Yamaguchi S, Tajino J, Zhang X, Akiyama H, Kuroki H. Optimum temperature for extracellular matrix production by articular chondrocytes. Int J Hyperthermia. 2014 Mar;30(2):96-101. PubMed PMID: 24499154.
3. Regenerative rehabilitation is an emerging field that a promising resource to maximize tissue regeneration and functional restoration in regenerative medicine. As co-investigator, I contributed to studies demonstrating that treadmill exercise and low-intensity pulsed ultrasound stimulation combined with mesenchymal stromal cell therapy could be a promising physical therapy for the treatment of the osteochondral defect in regenerative medicine.
a. Yamaguchi S, Aoyama T, Ito A, Nagai M, Iijima H, Tajino J, Zhang X, Wataru K, Kuroki H. Effect of Low-Intensity Pulsed Ultrasound after Mesenchymal Stromal Cell Injection to Treat Osteochondral Defects: An In Vivo Study. Ultrasound Med Biol. 2016 Dec;42(12):2903-2913. PubMed PMID: 27600474.
b. Yamaguchi S, Aoyama T, Ito A, Nagai M, Iijima H, Tajino J, Zhang X, Kiyan W, Kuroki H. The Effect of Exercise on the Early Stages of Mesenchymal Stromal Cell-Induced Cartilage Repair in a Rat Osteochondral Defect Model. PLoS One. 2016;11(3):e0151580. PubMed PMID: 26968036; PubMed Central PMCID: PMC4788414.
4. As co-investigator, I contributed to studies demonstrating that interventional physical exercise could prevent the progression of post-traumatic osteoarthritic changes in articular cartilage and subchondral in a pre-clinical rat meniscus injury model. Despite the lack of effective disease modifying therapies for OA, our work suggests that exercise intervention is a promising approach for preventing the progression of osteoarthritis after traumatic injury.
a. Iijima H, Ito A, Nagai M, Tajino J, Yamaguchi S, Kiyan W, Nakahata A, Zhang J, Wang T, Aoyama T, Nishitani K, Kuroki H. Physiological exercise loading suppresses post-traumatic osteoarthritis progression via an increase in bone morphogenetic proteins expression in an experimental rat knee model. Osteoarthritis Cartilage. 2016 Dec 10;PubMed PMID: 27965139.
b. Iijima H, Aoyama T, Tajino J, Ito A, Nagai M, Yamaguchi S, Zhang X, Kiyan W, Kuroki H. Subchondral plate porosity colocalizes with the point of mechanical load during ambulation in a rat knee model of post-traumatic osteoarthritis. Osteoarthritis Cartilage. 2016 Feb;24(2):354-63. PubMed PMID: 26376125.
c. Iijima H, Aoyama T, Ito A, Yamaguchi S, Nagai M, Tajino J, Zhang X, Kuroki H. Effects of short-term gentle treadmill walking on subchondral bone in a rat model of instability-induced osteoarthritis. Osteoarthritis Cartilage. 2015 Sep;23(9):1563-74. PubMed PMID: 25916553.
d. Iijima H, Aoyama T, Ito A, Tajino J, Nagai M, Zhang X, Yamaguchi S, Akiyama H, Kuroki H. Destabilization of the medial meniscus leads to subchondral bone defects and site-specific cartilage degeneration in an experimental rat model. Osteoarthritis Cartilage. 2014 Jul;22(7):1036-43. PubMed PMID: 24857975.
5. I was a co-investigator in a team that executed studies related to the effects of gravitational forces on gait motion in rats. This work was performed as a part of efforts to elucidate the influence of gravitational stimuli on the central nerve system. Our results demonstrated that simulated microgravity affects gait motion of rats through the central nervous system in addition to muscle and skeletal structures. Furthermore, we postulated that these central nervous system alterations could be attenuated by intermittent centrifugation, which had previously been applied to counteract the musculoskeletal effects of microgravity.
a. Tajino J, Ito A, Nagai M, Zhang X, Yamaguchi S, Iijima H, Aoyama T, Kuroki H. Intermittent application of hypergravity by centrifugation attenuates disruption of rat gait induced by 2 weeks of simulated microgravity. Behav Brain Res. 2015;287:276-84. PubMed PMID: 25819803.
b. Tajino J, Ito A, Nagai M, Zhang X, Yamaguchi S, Iijima H, Aoyama T, Kuroki H. Discordance in recovery between altered locomotion and muscle atrophy induced by simulated microgravity in rats. J Mot Behav. 2015;47(5):397-406. PubMed PMID: 25789843.
E. Additional Information: Research Support and/or Scholastic Performance
Ongoing Research Support
17K13052, JSPS KAKENHI (Grant-in-Aid for Young Scientists B)
Developing Novel Physical Therapy for Enhancing Peripheral Nerve Regeneration by Low-Intensity Pulsed Ultrasound.
Completed Research Support
15J06180, Grant-in-Aid for Japan Society for the Promotion of Science for Fellows (PD)
Articular cartilage regeneration using thermal stimulation
253611, Grant-in-Aid for Japan Society for the Promotion of Science for Fellows (DC2)
Study of the heat shock responses for the treatment of osteoarthritis
copyright Kuroki Laboratory