Can you give us an overview of your current clinical research and how you feel it is progressing?

Nakamura: In this trial, we aim to transplant approximately two million human iPS cell-derived neural progenitor cells (iPSC-NS/PCs) into spinal cord injury patients who are two to four weeks post-injury in the subacute phase, as well as patients with complete paralysis, targeting the epicenter of the injury. Over the next year, we will confirm the safety of the treatment by verifying that it does not give rise to tumors or other health concerns. We will also lead trial participants through the standard rehabilitation process that current patients receive to compare functional improvement with patients who have not received cell transplantation. We plan to include three more patients in this clinical trial, for a total of four. Now that we have successfully performed the procedure on the first participant, we have finally made real progress, but I also think that we have reached a new starting point.

Okano: By completing our first transplantation, I believe we've gone from zero to one. There is no time to waste. We can finally pick up the pace in bringing this procedure from the bench to the bedside, where we can treat patients.

Patients with a chronic spinal injury and their families also have high hopes for this procedure. What is the outlook for the treatment of those patients?

Okano: We are, of course, pursuing research on the chronic phase of injury as well. For these patients, we will use iPSC-NS/PCs that are slightly different from those we use for subacute-phase patients.

Nakamura: After our trial gained some media coverage, I received a letter from a family member of a chronic-phase patient who said, "My father had given up but has found renewed hope in rehabilitation after seeing this news.” I am grateful that our work has become a beacon of hope for both subacute-phase and chronic-phase patients, and I am more steeled in my determination than ever.

At public lectures and other events, I always emphasize the need for patients to continue rehab efforts and strive to keep the rest of their bodies operating at maximum capacity. Some spinal cord injury patients and their families mistakenly believe that iPS cells are magic cells and that if they receive them, they will suddenly be able to move their legs, but that is not how it works. Cell transplantation is just one piece of the spinal cord regeneration puzzle. Rehabilitation is another essential piece. This regenerative medicine is coming, but patients need to sustain muscle, strength, stamina, and energy through daily rehabilitation for the treatment to be effective.

What are some of the challenges to the practical application of regenerative medicine?

Okano: If we are to standardize regenerative medicine in the future and provide iPS cell-derived cells to every corner of the country, we must develop the infrastructure to cultivate cells in bulk and build large-scale cell culture facilities. Universities cannot take on this responsibility alone, nor can we assume success by simply leaving corporations to do the work. In other words, we need to work together through industry-academia partnerships and medical-industrial collaborations.

So now, in addition to our research work, Prof. Nakamura and I endeavor to gain national support for regenerative medicine through various forums, not least of which is the Japanese Society for Regenerative Medicine. If we can increase demand for regenerative medicine and create the system to supply that demand, we expect the increased scale will naturally lead to cost reductions.

Nakamura: If we want to make regenerative medicine affordable and available to patients everywhere, we must be able to provide better, faster, and cheaper products. To this end, it is essential to continue our scientific work and approach industry-academia partnerships with a sense of urgency.

What do you envision the future of regenerative medicine looking like?

Okano: Right now, we are primarily using iPS cell regenerative medicine to target debilitating and incurable diseases, but this medicine will eventually become a key player in the treatment of common diseases as well. I believe we will see a trend toward increased use of regenerative medicine combined with standard treatment further to enhance the effects of existing drugs and rehabilitation.

Nakamura: I want to see regenerative medicine help people live longer, healthier, and more active lives. Although medical advances have increased life expectancy, the reality is that our own organs and bodies often aren’t able to keep up with the technology. This is true in other fields, such as neurology for dementia and stroke and orthopedics for back and knee joint pain. If regenerative medicine can help combat these realities, more people will be able to live the lives that they want to the very end, rather than being confined to beds or requiring nursing care. I believe that contributing to this new society is the goal of regenerative medicine.

After two decades of working together, how would you describe each other as researchers?

Nakamura: Prof. Okano is a world-class neuroscientist for whom I have complete respect. To offer a specific example of his brilliance, we would often go to the ICM (Institut du Cerveau et de la Moelle, or Paris Brain Institute), and Prof. Okano would always have these rousing conversations with researchers from all different fields. I was genuinely amazed at the breadth and depth of his knowledge, wondering how he could know so much about so many things outside his expertise. In academic circles, people often ask how I've been able to keep up with someone as sharp as Prof. Okano for decades. I tell them I’m just winging it! [laughs]

Okano: It is rare to find an orthopedic surgeon with as much passion as Prof. Nakamura. I was in surgery with him the other day, and sure enough, he did a fantastic job. With his remarkable dexterity and fierce dedication, I have complete confidence in everything he does. It would be fair to say that Prof. Nakamura and I have different personalities, but that is probably why we have been able to work together so well for more than 20 years. [laughs]

Nakamura: Former Keio University President Shinzo Koizumi spoke of sports as an example where "practice makes the impossible possible." Through my research with Prof. Okano, I believe that "science makes the impossible possible.” Something thought impossible a few decades ago is now one step closer to reality. I’m driven to press on with my work now more than ever before.

What do you think sets the Keio School of Medicine apart?

Okano: Since its establishment, the Keio University School of Medicine has upheld the philosophy of uniting basic and clinical approaches. The barrier between the two is relatively low here. It's rare to find a university that can seamlessly manage translational research, which uses basic research to drive the development of new diagnostic and therapeutic methods, and reverse translational research, which uses the results of clinical practice and diagnoses to inform basic research. It is a great environment to work in.

Nakamura: I agree. Actually, in our approach to spinal cord regeneration, Prof. Okano handles the basic research side while I take the clinical. This tag-team approach is the epitome of the Keio School of Medicine ethos.

Okano: I think it's also worth noting that clinicians from several departments, including neurosurgery, neurology, and orthopedics, often come to our physiology laboratory. The ideas and examination methods of so many doctors from different specialties often prove quite helpful. We can formulate a collective strategy to fight disease by creating a clinical community. So not only is the barrier between basic and clinical low but so is the one between different clinical departments. I really think Keio has a lot to offer as a university.

Could you please offer a message to the next generation aspiring to study medicine?

Okano: The urge to use science to open up entirely new research fields and the desire to help people suffering from incurable diseases have been the driving forces behind my research. No matter what the future holds, new and intractable diseases will emerge. Conquer cancer or dementia, and the next contender will come along. I hope that the next generation will produce scientists and physicians who possess the wisdom and bravery necessary to develop the medicine needed to fight these diseases.

Nakamura: There are three words I often teach to medical students and young orthopedic surgeons. The first is “Passion.” Passion could be a hope or a dream, but whatever it is, you will need it to sketch your "Vision." Where do you want to be in ten years? Plan the next three years, the next five, and take the "Action" needed to make your vision a reality. Passion, Vision, Action. Embrace these ideas, and you can be forgiven even in failure. No matter how hard you fall, you'll find a way to pull yourself back up, stronger than before.

I want students to find something at university that they will be able to look back on and say that they gave their all. It doesn't matter if it's studying, club activities, or something else. Dive in and give it everything you've got because that kind of approach pays off in the future. I want to see young students bring their highest aspirations and boldest dreams to the Keio School of Medicine.

Hideyuki Okano

Professor Okano completed his Doctor of Medicine (M.D.) at the Keio University School of Medicine in 1983. After appointments at the Keio University School of Medicine’s Department of Physiology, Osaka University’s Institute for Protein Research, Johns Hopkins University in the U.S., and The University of Tokyo’s Institute of Medical Science, he became a Professor in the Department of Molecular Neurobiology at the University of Tsukuba in 1994. He moved to the Osaka University School of Medicine in 1997, serving as a professor in the Department of Neurofunctional Anatomy, Osaka University School of Medicine, before returning to the Keio University School of Medicine in 2001, where he has served as a professor in the Department of Physiology ever since. He has also served as Dean of the Keio University Graduate School of Medicine since 2017. He has received numerous awards and honors, including the Commendation for Science and Technology by the Minister of Education, Culture, Sports, Science and Technology, the Inoue Prize for Science, a Medal of Honor with Purple Ribbon, the Erwin von Bälz Prize, the Takamine Memorial Daiichi Sankyo Award, and the Uehara Prize.

Masaya Nakamura

Professor Nakamura completed his Doctor of Medicine (M.D.) at the Keio University School of Medicine in 1987. After appointments at the Keio University School of Medicine’s Department of Orthopedic Surgery and Georgetown University in the U.S., he returned to the Keio University School of Medicine to serve as an instructor. He also served as a Lecturer at the Kyoto University Institute for Life and Medical Sciences and the Department of Pharmacology in the Hoshi University Faculty of Pharmaceutical Sciences, as well as an Assistant Professor in the Keio University School of Medicine's Department of Orthopedic Surgery, where he has served as professor since 2015. He has received numerous awards, including the Japanese Orthopaedic Association Academic Encouragement Award, the Erwin von Bälz Prize, and the Japanese Society for Regenerative Medicine Award.