In the early 2000s, countries around the world engaged in a research competition over stem cells, dubbed "the flower of future medicine." South Korea got off to a fast start. In 2004, a team led by Dr. Hwang Woo-suk announced that it had successfully cultivated the world's first cloned embryonic stem cells. However, as this paper was revealed to be fabricated, South Korea fell behind, while Japan invested heavily in induced pluripotent stem cells (iPS cells), which eventually earned a Nobel Prize, and moved ahead. This article looks at how the stem cell competition between South Korea and Japan has progressed over the past 20 years.[Editor’s note]
The world is paying attention to Japan's succession of research and development (R&D) achievements in stem cell therapies. This is because the "induced pluripotent stem cells (iPS cells)" that Japan has heavily invested in have increased chances of solving intractable diseases such as Parkinson's disease. Analysts suggest that the day of fruition for the research efforts of Japanese scientists, coupled with significant investments from the government and corporations, is imminent.
◇Japan presents the possibility of treating Parkinson's disease
Parkinson's disease is a degenerative disorder in which nerve cells that secrete dopamine in the brain deteriorate, leading to a loss of motor function and tremors throughout the body. Severe cases can also lead to cognitive decline, but there are still no definitive treatments. Japanese scientists have proven that Parkinson's disease can be fundamentally treated using iPS cells.
iPS cells are induced to revert to an embryonic stem cell state capable of growing into any type of human cell by introducing specific genes, proteins, or chemicals into fully developed cells. Embryonic stem cells are obtained from fertilized eggs where sperm and eggs meet, while iPS cells avoid this and can sidestep bioethics controversies. One advantage is that therapies can be created from the patient's own cells, eliminating the need for immunosuppressants.
A research team from Kyoto University published a paper in the international journal Nature on the 17th, detailing the results of Phase 1 and Phase 2 clinical trials conducted on patients with Parkinson's disease. The clinical trials were carried out at Kyoto University Hospital involving seven patients aged 50 to 69. The iPS cells were differentiated into precursor cells for dopamine nerve cells, which were then transplanted into the brains of the seven patients (three receiving low doses and four receiving high doses) and followed up for 24 months.
The trial results indicated no safety issues. The researchers noted, "No significant side effects appeared to the level of major adverse effects such as tumor formation due to excessive growth of the transplanted cells." A total of 73 mild to moderate adverse reactions were reported. Furthermore, magnetic resonance imaging (MRI) showed no signs of excessive growth of the transplanted cells. Some patients also exhibited a reduction in tremors or rigidity, indicating therapeutic effects.
The Kyoto University research team stated, "We have demonstrated that the homogenous iPSC-derived dopamine precursor cells survive post-administration while producing dopamine, and importantly, do not form tumors," indicating potential safety and clinical efficacy against Parkinson's disease.
◇20 years of research relay… active clinical trials
Kyoto University initiated iPS cell research and is currently leading global research efforts. Professor Shinya Yamanaka of Kyoto University discovered in 2006 that injecting specific genes into mouse skin cells can create iPS cells similar to embryonic stem cells. For this achievement, he received the Nobel Prize in 2012.
With the publication of the latest Nature paper, academia predicts that Japan could become the first nation to officially approve iPS cell treatments for Parkinson's disease. On the same day, Nature commented that "after nearly 20 years of effort and trial and error in the field of stem cells, Japan has reached a "critical point" to introduce a stem cell therapy to market."
Although Japan was the first to open the stem cell therapy market, there is currently no officially approved iPS cell treatment. This is due to the lack of clear therapeutic effects verified in large-scale clinical trials and ongoing concerns about treatment expenses and safety.
Nevertheless, the reason many believe Japan can soon reap the benefits of its investments in stem cell therapy R&D is due to the ongoing advancement of research. According to Nature, over 60 iPS cell therapy clinical trials are currently being conducted worldwide, with about one-third taking place in Japan. The safety of these trials has generally been confirmed, and some have also observed significant therapeutic effects.
Since Professor Yamanaka won the Nobel Prize for his research on iPS cells, the Japanese government and academia have focused on investing in this field. Results have followed. In 2014, Dr. Masayo Takahashi from the RIKEN Center successfully transplanted retinal cells derived from iPS cells into patients, marking the world's first.
The transplanted cells survived for more than 10 years, maintaining the patient’s vision. However, creating therapies from autologous cells has proven time-consuming and expensive, making commercialization challenging. Dr. Masayo noted to Nature, "We are developing a method to create iPS cell therapies using cells from other individuals," emphasizing that "Japan's regenerative medicine is advancing very rapidly."
Professor Jun Takahashi from Kyoto University, who led the iPS cell treatment research for Parkinson's disease, has transferred the technology to the Japanese pharmaceutical company Sumitomo Pharma for commercialization and is now focusing on developing iPS cell treatments for strokes.
◇Japan’s bold investment… rapid approval system introduced
Japanese researchers have been able to continue their research achievements and conduct a "long-distance run" due to a solid policy and institutional foundation.
Since 2013, the Japanese government has decided to invest approximately 110 billion yen (about 1 trillion won) in regenerative medicine research over a period of 10 years. Most of this budget has been used to support research institutions such as Kyoto University's iPS Cell Research Institute. Even after the 10-year investment period ended in 2023, about 9 billion yen (approximately 895 million won) continues to be invested annually.
With the Japanese government providing significant support, large-scale investments from the private sector followed. Scientists are challenging clinical trial research and starting startups. Major biotechnology corporations made substantial investments in manufacturing facilities for cell therapies and opened medical facilities to accommodate patients from Japan and abroad.
In 2020, Tadashi Yanai, chairman of Fast Retailing, which operates the clothing company Uniqlo, donated 10 billion yen (approximately 1.123 billion won at that time) to Kyoto University for cancer immunity, stem cell, and coronavirus research. In 2018, Sumitomo Pharma completed the world's first facilities for producing iPS cell therapies. Dr. Masayo from RIKEN established a system using AI robots to produce iPS cell-based retinal cells that can treat over 800 patients within four months.
Japan not only provided investment but also established supportive systems. In 2013, Japan introduced a system that allows conditional use of stem cell and gene therapies in advance if their safety is confirmed and expected to be effective.
Medicines and medical devices must demonstrate efficacy and safety through clinical trials and receive official approval before they can be commercialized. However, for diseases lacking adequate treatment alternatives, this system allows for rapid patient treatment without having to undergo all clinical trial processes. Public insurance coverage has also been extended to regenerative medicine therapies, including gene and stem cell therapies, paving the way for R&D to translate into sales.
Nature remarked, "Overall, Japan is leading the way into the commercialization era of stem cell therapies and in the coming years, iPS-based treatments could become a transformative point in the lives of actual patients."
☞Stem cell
A type of primitive cell that can differentiate into various human cells. The term "adult stem cell" refers to those derived from adult bone marrow or adipose tissue, while "embryonic stem cells" are obtained from fertilized eggs remaining after infertility treatment, and "cloned embryonic stem cells" are derived from a cloned embryo created by fusing a fully developed cell and an egg. Induced pluripotent stem cells (iPS cells) are made by inserting specific genes into fully developed cells to create them in the embryonic stem cell state.
References
Nature(2025) DOI: https://doi.org/10.1038/s41586-025-08700-0
NEJM(2017) DOI: https://www.nejm.org/doi/10.1056/NEJMoa1608368
Nobel Prize(2012) https://www.nobelprize.org/prizes/medicine/2012/press-release/