20 Years of iPS Cells: Japan's Regenerative Medicine Revolution Reaches Historic Milestone
Introduction: The Day Biology Was Rewritten
On August 10, 2006, Professor Shinya Yamanaka and his team at Kyoto University published a groundbreaking paper in the prestigious journal Cell. By introducing just four genes (Oct3/4, Sox2, Klf4, and c-Myc) into mouse skin cells, they successfully created "induced pluripotent stem cells" (iPS cells) — cells capable of differentiating into any cell type in the body.
This discovery fundamentally overturned the biological dogma that differentiated cells could never return to a pluripotent state. The following year, in 2007, the team successfully created human iPS cells, and in 2012, Professor Yamanaka was awarded the Nobel Prize in Physiology or Medicine. The remarkably short six-year span between discovery and Nobel recognition underscores just how revolutionary this breakthrough was.
Now, in 2026, iPS cells mark their 20th anniversary. This milestone year brings Japan closer than ever to achieving the world's first regulatory approval for iPS cell-derived regenerative medicine products.
2025: A Landmark Year for Approval Applications
The year 2025 marked a pivotal turning point in the commercialization of iPS cell technology, with multiple companies filing for marketing authorization based on clinical trial results.
Parkinson's Disease Treatment: Sumitomo Pharma's Challenge
In August 2025, Sumitomo Pharma submitted a marketing authorization application to Japan's Ministry of Health, Labour and Welfare for "raguneprocel," an iPS cell-derived dopaminergic progenitor cell product for treating advanced Parkinson's disease.
Parkinson's disease is a debilitating condition caused by the loss of dopamine-producing neurons in the brain, leading to tremors, slowed movement, and impaired quality of life. As the disease progresses, medication becomes less effective, leaving patients with limited options.
A physician-led clinical trial conducted by Kyoto University's Center for iPS Cell Research and Application (CiRA) involved transplanting iPS cell-derived cells into the brains of seven Parkinson's patients aged 50-69. After 24 months of observation, no serious adverse events were reported, and four of six patients showed improvement in motor function. These results were published in the prestigious journal Nature in April 2025.
The product has been designated under Japan's "Sakigake" (Pioneering) expedited review program, meaning it will receive priority examination. A decision on approval could come as early as February 2026.
Heart Failure Treatment: Cuorips' Cardiac Muscle Sheets
Cuorips, a startup originating from Osaka University, also filed for marketing authorization in April 2025 for their "cardiac muscle sheet" to treat severe heart failure.
These sheets are created by processing iPS cell-derived cardiomyocytes into a 0.1mm-thick sheet format. When applied to hearts damaged by conditions like myocardial infarction, the sheets secrete factors that promote blood vessel regeneration and improve cardiac function.
Clinical trials led by Professor Yoshiki Sawa of Osaka University began in 2020, with cardiac sheets transplanted into eight patients with severe ischemic heart disease. Safety was confirmed in all patients, and more than half showed improvement in exercise capacity and cardiac function. Some patients even achieved social rehabilitation and returned to work.
Which Fields Are Most Advanced?
Research on iPS cell-based regenerative medicine spans numerous diseases. The fields closest to practical application include:
1. Ophthalmology (Retina and Cornea) — The Pioneer Field
In 2014, Dr. Masayo Takahashi and her team at RIKEN performed the world's first clinical surgery using iPS cells, transplanting retinal pigment epithelial cell sheets derived from iPS cells into a patient with age-related macular degeneration.
Since then, applications have expanded to retinitis pigmentosa, limbal stem cell deficiency, and other previously untreatable eye conditions. Professor Kohji Nishida's team at Osaka University completed the world's first clinical study transplanting iPS cell-derived corneal epithelial cell sheets, with safety confirmed in all four cases and one patient's corrected visual acuity improving from 0.15 to 0.7.
Sumitomo Pharma has also initiated clinical trials for retinitis pigmentosa in the United States, targeting patient enrollment in fiscal 2025.
2. Neurological Diseases (Parkinson's Disease and Spinal Cord Injury)
As noted above, Parkinson's disease treatment is in the final stages of the approval process.
For spinal cord injury, Professor Hideyuki Okano of Keio University has conducted clinical research transplanting iPS cell-derived neural progenitor cells into patients with subacute complete spinal cord injury. The first human transplant was performed in December 2021, with preliminary safety confirmed.
3. Cardiac Diseases (Heart Failure)
In addition to Cuorips' cardiac sheets, Heartseed, a Keio University spinoff, is advancing clinical trials of a therapy that injects "cardiac spheres" — clusters of iPS cell-derived cardiomyocytes — into damaged hearts.
Intensifying Global Competition
While iPS cells originated in Japan, international competition has become increasingly fierce.
According to Cell Stem Cell, 115 clinical trials using iPS and ES cells were conducted worldwide between 2010 and January 2025. By country, the United States accounts for 38%, China for 15%, and Japan for 12%.
Notably, iPS cell utilization has surged since 2020. While ES cells (embryonic stem cells) faced ethical concerns due to their derivation from fertilized eggs, iPS cells avoid this issue, accelerating research and development globally.
In the United States, massive private investment is flowing into iPS cell therapies, with venture companies launching clinical trials one after another. China has also made large-scale national investments, announcing achievements in iPS cell-based cardiac regeneration in 2023.
Professor Hideyuki Okano of Keio University warns that "Japanese regenerative medicine is at a critical juncture." The question now is whether Japan can leverage the regulatory framework it pioneered to achieve commercialization ahead of the world.
Challenges and Future Outlook
The "Conditional Approval" System
Japan has a unique regulatory framework called "conditional and time-limited approval" for regenerative medicine products. This allows "provisional approval" based on data from trials involving small patient numbers, provided certain safety and efficacy criteria are met. After approval, manufacturers continue collecting real-world data while working toward full approval.
Both Sumitomo Pharma and Cuorips are initially targeting this conditional approval. However, achieving full approval will require additional time and effort to accumulate more extensive safety and efficacy data.
Cost Challenges
iPS cell-derived products face high manufacturing costs, making pricing for widespread adoption a significant challenge. Cell cultivation requires advanced technology and specialized facilities, making the establishment of mass production systems an urgent priority.
The Kyoto University iPS Cell Research Foundation is advancing automation of clinical-grade iPS cell manufacturing, working toward future cost reductions.
Growth of the Regenerative Medicine Market
Japan's regenerative medicine market is projected to reach 1 trillion yen by 2030 and 1.6 trillion yen by 2040. The approval of iPS cell products holds significant implications for Japan's medical industry.
Conclusion: 20 Years of Progress and the Next Two Decades
Twenty years since their discovery, iPS cells have steadily progressed from basic research to clinical application. If the world's first approval is achieved in 2026, it will mark not an ending but a new beginning.
Professor Shinya Yamanaka has said, "It's only real when it helps patients in clinical settings." For patients suffering from intractable diseases, and for the future of Japanese science and technology, researchers' challenges continue.
iPS cell-based regenerative medicine is a field where Japan has led the world. What discussions about regenerative medicine and advanced medical treatments are taking place in your country? We'd love to hear about your expectations, concerns, and ethical perspectives on new treatment methods. Please share your thoughts!
References
- https://news.yahoo.co.jp/articles/af9cadb5b5713db3189dd450af5adaab2f3c62f4
- https://www.sumitomo-pharma.co.jp/news/20250805-2.html
- https://www.nikkei.com/article/DGXZQOUF2124A0R20C25A7000000/
- https://resou.osaka-u.ac.jp/ja/research/2024/20241108_4
- https://www.cira-foundation.or.jp/j/achievement/provision-of-ips-cells/
- https://www.nippon.com/ja/japan-topics/c15101/
- https://www.kyoto-u.ac.jp/ja/about/history/honor/award-b/nobel/2015/yamanaka
Reactions in Japan
20 years since iPS cells, and we're finally seeing practical applications. When Professor Yamanaka won the Nobel Prize, I thought treatments would come right away, but drug development really takes time. But it's been worth the wait.
Improvement in 4 out of 6 patients in the Parkinson's trial... honestly, I expected better numbers. I'm a bit worried about whether conditional approval is really enough.
Both Sumitomo Pharma and Cuorips are still aiming for 'provisional approval.' The road to full approval is long. But if Japan can be first in the world, we can lead in industrializing regenerative medicine. The country should support this fully.
Speaking as someone who treats Parkinson's patients, this is a ray of hope for those whose medications are becoming ineffective. It creates new possibilities for people whose only option was DBS.
Looking forward to seeing what happens to Cuorips' stock price if the cardiac sheet gets approved. Regenerative medicine stocks are definitely ones to watch.
The catching up by the US and China is remarkable. Even though this is Japanese technology, we're losing in the number of clinical trials. Just having regulations in place isn't enough. We need more research funding.
I nearly cried watching the news about the cardiac sheets. As someone waiting for a heart transplant, having more options like this is truly appreciated. I hope it gets approved.
The problem is cost. Even with insurance coverage, how much will patients pay for iPS cell products? If it's too expensive, it's just pie in the sky. Developing technology to reduce manufacturing costs is urgent.
It's moving to see how far Professor Yamanaka's research has come. I remember being shocked when I read the paper as a student. I hope this becomes an achievement that demonstrates Japan's research capabilities.
We have several Parkinson's patients at our facility. They're all managing daily life with medication, but if there's a fundamental treatment, I think it could really change their lives.
Isn't the number of trial participants too small? Is it really okay to approve with just 8 or 7 people? Part of me wants them to be more careful.
Having seen iPS research up close, I know how much effort it took to get here. Respect to everyone involved. And now the real work begins.
Visual acuity improving from 0.15 to 0.7 in the cornea clinical study... I can imagine how much life changes with just that. Thank you to the researchers.
The world is watching whether Japan's unique 'conditional approval' system works. Success becomes a model for other countries; failure strengthens criticism of deregulation.
Even if approved, only people in cities with university hospitals can actually receive treatment, right? I have mixed feelings about the widening medical gap with rural areas.
Will the prediction of a 1 trillion yen regenerative medicine market by 2030 come true? If iPS cell approval becomes a catalyst, Japan's entire bio industry will be revitalized. I'm hopeful.
iPS cell research is advancing in the US too, but it's impressive that Japan might get the world's first approval. The FDA takes time with approvals, so maybe Japan's regulatory system is working well.
As a neurologist, I have high hopes for applications in Parkinson's treatment. The potential to go beyond the limitations of drug therapy is groundbreaking. However, long-term safety data is still limited, so we need to watch carefully.
In China, iPS cell research is also progressing as a national project. Competition with Japan is fierce, but what matters most is that beneficial technology for patients becomes available worldwide. We need both competition and cooperation.
In Germany, ethical debates about stem cell research have continued for years. iPS cells don't use embryos, so that's clear, but if treatment costs are high, new ethical questions arise about who can access it.
A family member in the UK is fighting Parkinson's disease. If approval happens in Japan, clinical trials might accelerate in other countries too. I'm praying for success for patients worldwide.
Regenerative medicine research is advancing in Korea too, but Japan's iPS cell research seems to be one step ahead. Professor Yamanaka's achievements are truly great. I think they contribute to scientific development across Asia.
From Mexico. Medical technologies approved in developed countries often take years to reach our country. Even if successful in Japan, it makes me think about when patients in developing countries can benefit.
In the French healthcare system, introducing such advanced medicine requires both national approval and insurance coverage. Japan's 'conditional approval' system is an interesting approach. It might be useful as a reference for the EU.
I work at a biotech company in California. We feel competition from Japanese companies, but this field has huge room for growth. Japan's approval would be a positive signal for the entire market.
Interest in regenerative medicine is growing in India too. If Japanese technology is commercialized, similar treatments might become possible in India in the future. I look forward to possibilities for technology transfer and joint research.
In Sweden, access to healthcare is guaranteed by universal insurance, but the cost of such cutting-edge treatments is a major challenge. If Japan succeeds in reducing costs, it will be good news for patients worldwide.
From Australia. My father has heart disease, so I'm very attentive to news like this. Cardiac sheet technology is truly innovative. Even approval in faraway Japan gives me hope.
I'm a researcher in Italy. iPS cell research is active in the EU too, but we're behind Japan in the speed of clinical applications. Regulatory differences play a role, but there's much to learn from Japan.
From Egypt. There are many patients suffering from intractable diseases in the Middle East too. I hope Japan's advanced medical technology will reach our region someday. I hope for a day when medicine has no borders.
Honestly, I'm skeptical about iPS cell commercialization. It took 20 years just for the first approval? Other advanced medicine follows the same pattern—big expectations followed by slow progress. We shouldn't expect too much.
From Brazil. Investment in basic research is limited in our country. With countries like Japan developing advanced medicine, we may benefit in the future too. I want to believe that science has no borders.