The following is general information introducing research findings. Results reported in studies do not mean the same outcome for any individual, and most of these studies are small or early-stage.
Summary — Japan was one of the first countries to establish a dedicated legal framework for regenerative medicine. Since November 2014, regenerative medicine provided by medical institutions has been governed by the Act on the Safety of Regenerative Medicine, and regenerative medical products manufactured and sold by companies by the Pharmaceuticals and Medical Devices Act. The latter includes a conditional, time-limited approval pathway that allows marketing once efficacy is presumed, under which stem cell products, for example for spinal cord injury (2018), have been approved.
Why Japan built its framework early
After Professor Shinya Yamanaka's team at Kyoto University first reported iPS cells in 2006 and received the 2012 Nobel Prize in Physiology or Medicine, Japan moved to develop regenerative medicine as a national research and industrial field. At the same time, safety problems arising from poorly evidenced cell therapies offered as self-pay care were raised. Against this background, regenerative medicine laws were enacted in 2013 and came into force in November 2014. The framework has two aims: speeding the practical use of regenerative medicine and managing the safety of cell therapies offered by medical institutions.
Two regulatory tracks
- Act on the Safety of Regenerative Medicine — covers care in which a medical institution, under a physician's responsibility, collects and processes cells and provides them to patients. Both research use and clinical use (mostly self-pay care not covered by insurance) must follow its procedures.
- Pharmaceuticals and Medical Devices Act — covers approval of 'regenerative medical products' manufactured and sold by companies. Based on clinical trial data, products are reviewed by the Pharmaceuticals and Medical Devices Agency (PMDA) and approved by the Ministry of Health, Labour and Welfare, and approved products can be covered by public health insurance.
Three risk classes under the regenerative medicine act
| Class | Typical examples | Review |
|---|---|---|
| Class I (high risk) | Cells derived from iPS or ES cells, gene-modified cells, animal cells, etc. | Certified special committee, followed by a Ministry review procedure |
| Class II (medium risk) | Somatic stem cells such as mesenchymal stem cells | Certified special committee for regenerative medicine |
| Class III (low risk) | Processed somatic cells that are not stem cells, etc. | Certified committee for regenerative medicine |
A medical institution must prepare a 'plan for the provision of regenerative medicine' describing the care, safety measures and how explanation and consent are handled, have it reviewed by the relevant committee and submit it to the Ministry. Facilities that culture or process cells also need separate licensing or notification. After provision, there are obligations to report adverse events and to report regularly, and some information from submitted plans is published. Exact criteria are set out in the law and Ministry materials and may change with amendments.
The conditional, time-limited approval pathway
Because the properties of the source cells of regenerative medical products vary from person to person, proving efficacy in large clinical trials as for ordinary drugs can take a long time. Japan therefore created a pathway that allows marketing with conditions and a time limit (up to seven years) once safety is confirmed and efficacy is 'presumed', requiring data confirming efficacy to be submitted within that period; if efficacy is not confirmed in time, approval is not maintained. The pathway is credited with enabling faster patient access, but also criticised for allowing marketing before evidence is sufficient.
Key cell products approved in Japan
- Autologous cultured epidermis (2007) — cultured from the patient's own skin cells, for conditions such as severe burns
- Autologous cultured cartilage (2012) — for conditions such as traumatic cartilage defects
- Allogeneic mesenchymal stem cells (2015) — for acute graft-versus-host disease (GVHD) after haematopoietic stem cell transplantation; Japan's first allogeneic mesenchymal stem cell product
- Autologous skeletal myoblast sheets (2015, conditional) — for severe heart failure, based on Osaka University research
- Autologous bone marrow-derived mesenchymal stem cells (2018, conditional) — for spinal cord injury, based on Sapporo Medical University research
- Allogeneic bone marrow-derived cells (2024, conditional) — for chronic motor paralysis after traumatic brain injury
Provision plans versus approved products
Submitting a provision plan under the regenerative medicine act means the review and notification procedures set by law have been followed; it does not mean the state has recognised the care as effective. Products approved under the Pharmaceuticals and Medical Devices Act, by contrast, have had their efficacy and safety reviewed on the basis of clinical trial data. A 2018 commentary in Nature highlighted the sale of unproven stem cell interventions in many countries, and the ISSCR publishes international guidelines on the clinical translation of stem cells. Distinguishing which system a given treatment falls under is the starting point for understanding its level of evidence.
How to check published information
Information on Japan's regenerative medicine system can be checked directly in public-agency materials. The text of the laws is available on the Japanese government's legal database (e-Gov), and an overview of the system, lists of committees and related notices on the Ministry of Health, Labour and Welfare's regenerative medicine page. Regenerative medicine carried out as research under the act, and clinical research, are registered in the Japan Registry of Clinical Trials (jRCT) operated by the Ministry, where the purpose, participants, methods and institutions of each study are published.
Review reports and package inserts for approved regenerative medical products are published through the Pharmaceuticals and Medical Devices Agency (PMDA), so the clinical trial data behind an approval and its conditions can be checked. Checking such public sources directly helps in understanding under which system, and on what evidence, a given form of care is provided.
The above summarises published papers and public-agency materials. University and institute names are given to identify research sources, not to introduce or recommend any medical institution.
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References
- 再生医療等の安全性の確保等に関する法律（平成25年法律第85号）— e-Gov 法令検索 https://laws.e-gov.go.jp/law/425AC0000000085
- 厚生労働省「再生医療について」 https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/kenkou_iryou/iryou/saisei_iryou/index.html
- Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663-676. View on PubMed
- Sipp D, Robey PG, Turner L. Clear up this stem-cell mess. Nature. 2018;561(7724):455-457. View on PubMed
- International Society for Stem Cell Research (ISSCR). Guidelines for Stem Cell Research and Clinical Translation (2021). https://www.isscr.org/guidelines
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