SPONSOR FEATURE

TRI www.tri-kobe.org

SPONSOR FEATURE Translational Research Informatics Center (TRI) takes the initiative to reduce disability through Japanese academic research

he Translational Research Informatics a major function of mesenchymal stem cells4, Center (TRI) was founded in 2002 by Damage → Signaling for example. The tissue is then regenerated and ↓ the Japanese Ministry of Education, Necrosis repaired. This action in particular is attributed T ↓ Mobilization Culture, Sports, Science and Technology ↓ to muse cells, which were first reported by Inflammation 5 (MEXT) and Kobe city as the first academic Homing Mari Dezawa of Tohoku University . Tissue data centre for clinical research in Japan. Since ↓ regeneration and clearance of abnormal its establishment, the TRI has led academic Conditioning cells maintain homeostasis in the adult body translational research and conducted clinical Clearance (Figs 1 and 2). A series of recent discoveries has studies (http://www.tri-kobe.org/). The TRI has ࣭anti inflammatory been made concerning the molecular entities succeeded in forming the Academic Research ࣭trophic action involved in the cellular processes of stem-cell ࣭ Organization with 14 active translational vascularization physiology and pathology. The technology ࣭ research centres. The TRI supports the whole others for repairing injuries and promoting cellular ↓ spectrum of clinical trials and clinical studies, differentiation and long-term regeneration Differentiation from phase 1 to phase 4, including many Regeneration using stem cells is unlike organ transplantation mega-trials and large cohort studies. Our — tissue is regenerated, rather than introduced. vision is to increase and promote biomedical Figure 1. Cellular processes at the foundation of An understanding of the body’s intrinsic innovation, and to accelerate the formation stem-cell physiology and pathology. mechanisms for maintaining optimum of a global alliance network. (For more, see health is revolutionizing the treatment of http://www.nature.com/naturejobs/science/ self-organization, field theory, symbiosis and intractable diseases. articles/10.1038/nj0417) resonance/synchrony. From these axioms we In summary, regenerative medicine using can get to the root of the three fundamental adult stem cells is an axiomatic technology in the The scientific revolution mysteries of life: origin and evolution, lifespan sense that it exploits natural healing mechanisms The scientific revolution that began with Galileo and consciousness. With these axioms in that are intrinsic to the body and that have been radically transformed society through numerous mind, we should be able to develop a better well conserved throughout evolution, and it advances that began with the development of a understanding of the true essence of the has the potential to become a fundamental methodology for the mathematical description revolution in stem-cell medicine. curative therapy. of nature by observation and experimentation. Ultimately, it gave rise to the civilization we live Stem-cell physiology and Status of clinical trials and in today. We are currently in the middle of an pathology development in regenerative unprecedented scientific revolution that will A deeper understanding of the physiology medicine undoubtedly prove to be the biggest paradigm and pathology of stem cells will facilitate and In Japan, the Pharmaceutical Affairs Law (PAL) shift in history1. Scientists are embracing fields pave the way for their clinical application. In was amended and enforced in 2014, to include a such as information technology and artificial order to maintain homeostasis at an individual review system for the consideration of the special intelligence (AI), genomics and molecular level, multicellular organisms must routinely characteristics of cellular and gene-therapy immunology, cybernetics and robotics, and eliminate not only dead cells, but also bacteria, products. This system accelerated regulatory nanotechnology and stem-cell medicine. viruses, infected cells and tumour cells. Innate approval for products with proven safety and Ray Kurzweil predicts that we will reach the immunity has a central role in this process. presumed efficacy, even if this had been shown singularity2, the point when AI surpasses human Removal of foreign bodies and abnormal cells by in a small number of patients, provided that the intelligence, around 2045. But because this immune cells such as natural killer (NK) cells and product is later tested in additional patients and singularity is likely to come as a massive wave phagocytes is a well-known mechanism. Recent another application for approval is submitted that integrates innovative technologies in AI studies have shown that innate immunity is also within a set period of time. Autologous human as well as in other fields, we may reach it faster involved in tissue regeneration3. Furthermore, skeletal myoblast sheets, developed by Yoshiki than Kurzweil has predicted. To ascertain the when the body detects abnormalities such as Sawa of Osaka University, were approved true essence of this extraordinary scientific tissue damage, adult stem cells are mobilized through this system. At around the same time, an revolution we require a profound understanding from their niches to the site of damage at which allogeneic human bone marrow mesenchymal of the structure and principles of such a range of cellular activities occur to correct stem cell (BM–MSC) product was also approved revolutions3. To that end, six axioms of life can aid the abnormality. The suppression of excessive under the amended law — the first allogeneic understanding. These are integrity, homeostasis, inflammatory responses has been shown to be cellular product.

SPONSOR RETAINS SOLE RESPONSIBILITY FOR CONTENT SPONSOR FEATURE

Self-preserva�on ability The fact that we are now seeing dramatic recoveries in those treated with stem-cell therapy, even in patients with severe conditions Microbes who were otherwise unlikely to make a recovery, Injury such as those with a spinal cord injury or cerebral Regenera�on and repairReconstruc�on (regenera�on) infarction, has overturned preconceptions. This

disruptive innovation will supplant conventional SPONSOR FEATURE technologies and result in the fundamental Cell damage/ transformation not only of treatments, but also Cell death of research and development of pharmaceutical products and medical devices, as well as research in regenerative medicine and biology. Clearance Degenera�on Pharmaceutical companies have invested Self-non-self recogni�on vast amounts of money and resources in the Prionoid Infarct Neoplasm Invasion development of many pharmaceutical products to treat disease. We have now entered an era of Figure 2. Mechanisms regulating maintenance of normal functioning of multicellular symbiotic systems. treatment that uses cellular mechanisms hidden To further accelerate product development, recovery and rehabilitation. The therapeutic within our own bodies. We are fast approaching the Japanese government started the SAKIGAKE effects of BM–MSC in animal models of stroke a day when disruptive innovation in stem-cell designation system in 2015 (ref. 6), which is also suggests neuronal plasticity. Thus, stem medicine turns conventional medical concepts similar to the US Food and Drug Administration’s cells and interactive biofeedback are both and values on their heads. Fast Track. This system cuts the review time mechanisms that govern the body as a unit REFERENCES for breakthrough drugs and devices in half by and as a multicellular complex system; they are 1. Kurzweil, R. The Singularity Is Near: When designating products for priority handling at also the fundamental systems for maintaining Humans Transcend Biology (Viking, 2006). the early stages of the consultation and review homeostasis and the integrity that is intrinsic to 2. Kuhn, S. T. The Structure of Scientific process. This has enabled the country to quickly the body, which has evolved great precision. The Revolutions (Univ. Chicago Press, 1962). 3. Schwartz, M. & Baruch, K. The resolution of deliver cutting-edge treatments to patients. approach of exploiting optimum regulation of neuroinflammation in neurodegeneration: Currently, three cellular and gene-therapy the overall system is now at medicine’s disposal. leukocyte recruitment via the choroid plexus. products have been designated through the This approach was pioneered by stem-cell EMBO J. 33, 7–22 (2014). SAKIGAKE system. All of these were promising therapy and the robot suit HAL — developments 4. Bernardo, M. et al. Mesenchymal Stromal technologies developed from basic research that will undoubtedly lead to a radical revolution Cells: Sensors and Switchers of Inflammation. conducted in academia. Autologous BM–MSC in medicine. These two technologies could Cell Stem Cell 13, 392–402 (2013). to treat spinal cord injury, developed by Osamu substantially reduce the number of people who 5. Uchida, H. et al. Transplantation of Unique Honmou7, is included in such products. These are confined to bed or using a wheelchair within Subpopulation of Fibroblasts, Muse Cells, products could potentially obtain regulatory five to ten years. Ameliorates Experimental Stroke Possibly via Robust Neuronal Differentiation Stem Cells approval within a few years. 34, 160–173 (2016). This is a typical example of disruptive The path towards reducing 6. Ministry of Health, Labour and Welfare. 8 innovation . Autologous stem-cell therapy is a disability Strategy of Sakigake http://www.mhlw. biological treatment that is completely different Advances in stem-cell physiology are sparking go.jp/english/policy/health-medical/ from conventional small molecule drugs; stem- discoveries about how the body repairs and pharmaceuticals/140729-01.html cell therapy exploits principles of the body’s regenerates itself after injury and what cells 7. Honmou, O. et al. Intravenous administration natural healing and regeneration processes and are involved in that process. Regenerative- of auto serum-expanded autologous has upended conventional treatment concepts. medicine clinical trials based on research mesenchymal stem cells in stroke Brain 134,1790–1807 (2011). Another example of disruptive innovation is at academic institutions using adult stem 8. Christensen, M. C. The Innovator’s Dilemma: the use of the interactive biofeedback principle cells are steadily progressing, and the day is When New Technologies Cause Great Firms to 9 for the robot suit HAL . This was developed by approaching when these products will become Fail (Harvard Business School Press, 1997). Yoshiyuki Sankai of University of Tsukuba and the first-line treatment for their indications. 9. Suzuki, K. et al. Intention-based walking Takashi Nakajima of Niigata National Hospital Japan is at the forefront of this field of research, support for paraplegia patients with Robot have conducted a multicenter clinical trial and preparations are being made for clinical Suit HAL. Adv. Robot. 21, 1441–1469 (2007). (JMA-IIA00156) for HAL to improve motor development abroad after regulatory approval 10. Sczesny-Kaiser, M. et al. HAL® exoskeleton neuron function. This accomplishment, as part within the country. The establishment of training improves walking parameters and of the Rare/Intractable Disease Project of the investigator-initiated IND-registered trials, normalizes cortical excitability in primary somatosensory cortex in spinal cord injury Ministry of Heath, Labour and Welfare was regulatory strategy consultations and the patients. J. Neuroeng. Rehabil. 12, 68 (2015). realized by unraveling the principles of the SAKIGAKE designation system were needed reciprocal physiological interaction between to support the development of promising AUTHORS the brain and muscles, which helped the technologies based on basic science conducted Masanori Fukushima researchers to reconstruct the connectivity at academic institutions. This is Japan’s new Director and Chairman of the TRI of neurons and represent plasticity10. In other road for generating innovation in health and Yasuko Kimura words, interactive biofeedback can drastically medicine, and it has made it possible to develop Senior Researcher of the TRI change conventional methods for functional products for approval more efficiently. E-mail: [email protected]

SPONSOR RETAINS SOLE RESPONSIBILITY FOR CONTENT