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. In fact, the product was approved on March 6, 2026 under the brand name Amshepli (a conditional, time-limited approval), becoming the world's first approved iPS-cell-derived regenerative medicine product.

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.

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!

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