On March 6, the Ministry of Health, Labour and Welfare (MHLW) gave conditional, time-limited approval to two regenerative medicine products made using induced pluripotent stem cells (iPS cells). One product targets patients with severe heart failure and the other targets those with Parkinson's disease. This marks the world's first approval of treatment products using iPS cells, a technology "born in Japan." Both products are expected to be used in medical settings before the end of the year.
iPS cells are cells in which several genes are artificially incorporated into cells such as skin cells, giving them the ability to change into various cells and tissues in the body. It has been about 20 years since Professor Shinya Yamanaka and his colleagues at Kyoto University reported the creation of these cells in mice in 2006. Japan is now ahead of the rest of the world in turning regenerative medicine into standard medical care, and clinical trials are moving forward for diseases beyond those targeted in this round of approvals. For patients, this means more treatment options, and expectations are rising for the arrival of new therapies.
Provided by Professor Shinya Yamanaka, Kyoto University and JST
Developed by a university spinoff and a research-driven company
The MHLW gave its formal approval after a ministry expert panel agreed on February 19 to approve the two products on a conditional, time-limited basis. The approved products are "ReHeart" developed by "Cuorips" (Tokyo), an Osaka University venture, and "Amchepry" developed by "Sumitomo Pharma" (Osaka), an R&D-oriented pharmaceutical company in the Sumitomo Chemical Group.
ReHeart targets severe heart failure caused by "ischemic cardiomyopathy," a condition in which the coronary arteries that carry oxygen and nutrients to the heart become narrow or blocked, leaving the heart muscle starved of blood and causing heart function to decline. Heart muscle cells made from another person's iPS cells are grown in a sheet, which is then attached to the surface of the heart to take hold and form new blood vessels. In the clinical trial, eight patients received the transplant, and all of them showed a reduction in symptoms and improvement in heart function.
Amchepry targets Parkinson's disease, which develops when the nerve cells in the brain that release the neurotransmitter dopamine decrease in number. Cells grown from another person's iPS cells into an early stage of dopamine-producing nerve cells are transplanted into the patient's brain. In the clinical trial, seven patients received the transplant, and of the six whose response could be evaluated, all were confirmed to have actually produced dopamine.
Because the number of cases in the clinical trials for both products was small, the MHLW's expert panel and the ministry itself applied a system that "allows early approval on a conditional, time-limited basis when safety has been confirmed and effectiveness can be reasonably assumed." The condition is that effectiveness must be confirmed through actual treatment within the seven-year approval period, after which unconditional approval can be sought.
Provided by Sumitomo Pharma
Many researchers overcome challenges and move toward practical application
Regenerative medicine products built on the groundbreaking work of Yamanaka, who received the Nobel Prize in Physiology or Medicine in 2012, have been put to practical application for the first time in the world. Extraordinary efforts have been made by researchers and development personnel to overcome several challenges.
While expectations for regenerative medicine using iPS cells grew from the outset, concerns about safety were also raised. A leading example was the possibility that tissue derived from iPS cells could become cancerous. If undifferentiated iPS cells remain when the tissue is transplanted, they may become cancerous. Although rejection is unlikely to occur because the transplanted cells are the patient's own, it is also necessary to carefully check for actual rejection.
On the concern about cancer, an MHLW research team analyzed the genomes of iPS cells in 2016 and put out a position that transplantation should be avoided if genetic mutations that could be linked to cancer formation are found. In response to these concerns and challenges, researchers at Kyoto University's Center for iPS Cell Research and Application (CiRA), to which Yamanaka belongs, and many other universities and research institutes in Japan have achieved results while confronting these issues.
In 2014, a RIKEN led group succeeded in the world's first surgery to transplant retinal cells of the eye created from iPS cells into a patient. Osaka University and Keio University pioneered research on its application to heart disease. In 2016, a research group at Shinshu University and other universities announced that they had succeeded in restoring heart function by transplanting it into a monkey with a myocardial infarction.
Meanwhile, in 2016, a research group from Hokkaido University and Keio University announced that they had elucidated the function of a gene that prevents iPS cells from becoming cancerous using a naked mole-rat, which is resistant to cancer. In 2017, Kyoto University announced that it had developed a method to remove cells at risk of cancer. There was also collaboration with various research institutes and universities for the "practical application of safe regenerative medicine."
Provided by Hokkaido University
Challenges remain: Diabetes, spinal cord injury, cancer, and more
As practical application research at many institutions moved steadily forward, Cuorips applied to the MHLW in April 2025 for approval to manufacture and sell ReHeart for severe heart failure, and Sumitomo Pharma applied in August 2025 for approval of Amchepry for Parkinson's disease.
The two forerunning products were the first to be submitted for approval, and the approval has recently been granted. Meanwhile, research into regenerative medicine applications for many other diseases is also steadily progressing.
According to the MHLW and other sources, clinical trials aimed at approval as regenerative medicine products and clinical research in preparation for clinical trials are progressing for age-related macular degeneration (RIKEN and others), type 1 diabetes (Kyoto University), aplastic anemia (Kyoto University), traumatic spinal cord injury (Keio University), corneal epithelial stem cell deficiency (Osaka University and others), and more.
It is also expected to be applied to cancer treatment. In January, Chiba University Hospital and RIKEN announced that in a clinical trial in which "natural killer T (NKT) cells" that attack cancer were made from iPS cells and given to patients with head and neck cancer, tumors shrank in 2 out of 8 patients. In addition, several other cancer treatment applications continue to be challenged, including ovarian cancer (CiRA and National Cancer Center Hospital East).
Provided by Chiba University Hospital and RIKEN
Yamanaka: "Move forward carefully and steadily"
At a press conference after the cabinet meeting on March 6, MHLW Minister Kenichiro Ueno expressed his hopes for the significance of this approval: "I hope this will bring relief to patients not only in Japan but also around the world." However, this time, the approval is only conditional and time-limited, and additional data must be collected within the respective time limits to finally prove efficacy and obtain "full approval".
Provided by the MHLW
In order for iPS cell-derived medicines to be used in a wide range of medical fields in the future, careful verification of the safety and efficacy of the two preceding cases is essential. Yamanaka, who currently serves as Honorary Director of CiRA, made the following comment when the ministry's expert panel agreed to the approval:
"I am very happy that, at the milestone of 20 years since we reported mouse iPS cells, we have been able to take a big step toward real-world use. However, to establish this as medicine, a process of confirming safety and effectiveness in many more cases from here is essential. I believe it is important to continue to move forward steadily, one step at a time, with scientific prudence, without getting carried away."
Photo taken by the author on January 2016
(UCHIJO Yoshitaka / Science Journalist)
Original article was provided by the Science Portal and has been translated by Science Japan.