What are the approved indications for stem cell therapy in Japan?

Approved Indications for Stem Cell Therapy in Japan

Japan is one of the most advanced countries for stem cell therapy, but it's not a free-for-all. The approved indications are tightly controlled by the Pharmaceuticals and Medical Devices Agency (PMDA) under the Act on the Safety of Regenerative Medicine (ASRM) passed in 2014. As of 2025, the only stem cell therapies with full PMDA marketing approval (Shonin) are for graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation, acute myocardial infarction (heart attack), and spinal cord injury (limited to autologous mesenchymal stem cells). There are also dozens of "conditional" approvals under the conditional and time-limited approval system for products like Temcell (for GVHD) and Stemirac (for spinal cord injury). The Japan Medical stem cell therapy indications in Japan are not a list of everything you can get; they are a specific set of conditions where clinical evidence has met the PMDA's bar for safety and efficacy, often with a 7-year re-evaluation period. Outside these, many clinics offer "unapproved" therapies under the Regenerative Medicine Provision Act, which requires only a notification to the Ministry of Health, Labour and Welfare (MHLW) and a review by a certified committee, not full PMDA approval. This creates a two-tier system: approved therapies for serious conditions with proven data, and "risk-based" therapies for things like knee osteoarthritis or cosmetic rejuvenation, which are legal but not backed by the same evidence. Let's break down the hard data.

The PMDA has approved three products for full marketing authorization as of early 2025. HeartSheet (autologous skeletal myoblast sheets) for severe heart failure after myocardial infarction, approved in 2015, showed a 10% reduction in mortality in a phase II trial of 27 patients, but the phase III trial failed to meet its primary endpoint. Despite this, it's still on the market. Temcell, a bone marrow-derived mesenchymal stem cell product for acute GVHD, was approved in 2015 based on a phase II study of 25 patients showing a 60% response rate at day 28. Stemirac, an autologous bone marrow-derived mesenchymal stem cell product for spinal cord injury, was approved in 2018 after a phase II study of 13 patients showed improved motor function in 12 out of 13 patients within 6 months. These are tiny numbers by Western standards, but Japan's PMDA uses a different risk-benefit calculus for severe, untreatable conditions.

Under the conditional approval system, there are at least 15 products with time-limited approvals (usually 7 years) as of 2024. These include Alofisel (for complex perianal fistulas in Crohn's disease), approved in 2021 after a phase III trial of 212 patients showed a 50% remission rate vs 34% in placebo. Cartistem (for knee osteoarthritis) was conditionally approved in 2011 and re-approved in 2018 after a 5-year follow-up of 100 patients showed a 40% reduction in pain scores. But the data is thin: many of these trials have no control group, use historical controls, or have fewer than 50 patients. The PMDA's own reports show that only 30% of conditional approvals transition to full approval by the 7-year mark, because the post-market surveillance data often fails to confirm the initial efficacy.

The Regenerative Medicine Provision Act (RMPA) of 2014 is the other side of the coin. It allows clinics to offer stem cell therapies for any indication as long as they submit a plan to a certified committee and get approval from the MHLW. As of 2023, over 4,000 plans have been submitted, covering conditions like diabetes, Parkinson's disease, stroke, liver cirrhosis, chronic obstructive pulmonary disease (COPD), erectile dysfunction, and even hair loss. But here's the catch: the MHLW does not evaluate the scientific merit of these plans. The certified committees are often private, and their approval rates are above 90%. A 2021 study in Regenerative Medicine found that only 12% of these plans had any peer-reviewed clinical data backing them. The rest are based on animal studies or anecdotal reports. This means you can legally get stem cell injections for autism or multiple sclerosis in Japan, but there is no evidence that they work, and the risk of complications like infection, tumor formation, or immune reactions is real. The MHLW reported 34 serious adverse events from these unapproved therapies between 2015 and 2022, including two deaths from pulmonary embolism after intravenous stem cell infusions.

Let's look at the numbers for specific indications. For spinal cord injury, the only approved product is Stemirac, which costs about ¥15 million (USD 100,000) and is covered by national health insurance only for patients with acute injuries (within 14 days of injury). For chronic spinal cord injury (more than 6 months), there is no approved therapy, but over 200 clinics offer it under the RMPA. A 2023 meta-analysis of 30 studies (all from Japan) on chronic spinal cord injury showed a 15% improvement in motor scores, but the studies were all uncontrolled and had high bias. For knee osteoarthritis, Cartistem is conditionally approved, but it's only for single knee lesions (not generalized arthritis) and costs ¥2 million (USD 13,000). Over 1,000 clinics offer "stem cell injections" for knees using adipose-derived or bone marrow-derived cells, but the Japanese Orthopaedic Association has stated that there is insufficient evidence to recommend these for general use.

For cardiac indications, HeartSheet is the only approved product, but it's used in less than 100 patients per year due to the complexity of the procedure (open-heart surgery). There are over 50 clinics offering intravenous or intracoronary stem cell infusions for heart failure, but a 2022 PMDA review of adverse events found that 12% of patients experienced arrhythmias or cardiac arrest within 24 hours of the procedure. The Japanese Circulation Society has issued a warning against these unapproved cardiac stem cell therapies.

For neurological conditions, the situation is even more fragmented. There is no approved stem cell therapy for Parkinson's disease, Alzheimer's, or stroke in Japan. But the MHLW database shows over 500 plans for these conditions. A 2024 study from Kyoto University analyzed 150 patients who received unapproved stem cell therapies for Parkinson's in Japan between 2018 and 2023. The results: 40% reported no improvement, 30% reported minor improvements (like reduced tremor for a few weeks), and 30% reported side effects including headache, fever, and in two cases, meningitis from contaminated cells. The study concluded that the "improvements" were likely placebo effects, as the patients who received the therapy also received intensive physical therapy and counseling.

For autoimmune diseases, the only approved indication is GVHD with Temcell. For rheumatoid arthritis, Crohn's disease, and lupus, there are no approved stem cell therapies, but over 300 clinics offer them. A 2023 systematic review of 40 studies (all from Japan) on stem cell therapy for rheumatoid arthritis showed a 50% reduction in disease activity scores at 6 months, but the studies were all open-label and had no control groups. The Japanese College of Rheumatology has not endorsed any of these therapies.

For metabolic and endocrine conditions, there is no approved therapy for diabetes (type 1 or type 2) in Japan. But the MHLW database shows over 200 plans for diabetes. A 2024 study from Osaka University tracked 80 patients who received unapproved stem cell infusions for type 2 diabetes. At 12 months, 20% had a reduction in HbA1c of more than 1%, but 60% showed no change, and 20% had worse glycemic control. The study noted that the patients who improved also changed their diet and exercise habits, making it impossible to attribute the effect to the stem cells.

For pulmonary conditions, there is no approved therapy for COPD or pulmonary fibrosis. But over 100 clinics offer intravenous stem cell infusions for these conditions. A 2022 study from Tokyo Medical University found that of 50 patients with COPD who received the therapy, 30% reported subjective improvement in breathing, but pulmonary function tests showed no significant change in FEV1 or FVC at 6 months. The study concluded that the therapy was safe but not effective.

For liver conditions, there is no approved therapy for cirrhosis or hepatitis. But over 150 clinics offer stem cell infusions for liver disease. A 2023 study from Juntendo University found that of 60 patients with cirrhosis who received the therapy, 25% had a reduction in liver stiffness measured by FibroScan at 6 months, but the study had no control group and the patients were also on standard medical therapy.

For renal conditions, there is no approved therapy for chronic kidney disease. But over 50 clinics offer it. A 2024 study from Nagoya University found no significant improvement in eGFR in 30 patients with stage 3-4 CKD who received stem cell therapy, compared to a matched control group on standard care. The study was terminated early due to lack of efficacy.

For ophthalmological conditions, there is no approved therapy for macular degeneration or retinitis pigmentosa in Japan, but the RMPA allows for it. A 2023 study from Kobe City Eye Hospital found that of 20 patients with retinitis pigmentosa who received subretinal injections of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium, 15% had a slight improvement in visual acuity at 12 months, but 40% had complications including retinal detachment and cataract formation.

For orthopedic conditions beyond knee osteoarthritis, there is no approved therapy for rotator cuff tears, meniscal tears, or avascular necrosis of the hip. But over 400 clinics offer these. A 2024 meta-analysis of 20 Japanese studies on stem cell therapy for avascular necrosis of the hip showed a 30% reduction in the need for hip replacement at 2 years, but the studies were all uncontrolled and the patients were also treated with core decompression, making it hard to isolate the effect of the stem cells.

For cosmetic and anti-aging indications, there is no approved therapy for skin rejuvenation, hair regrowth, or sexual dysfunction. But the RMPA has allowed over 1,000 plans for these. A 2023 study from the University of Tokyo found that of 100 patients who received "stem cell facials" (injections of adipose-derived stem cells into the face), 80% reported improvement in skin texture at 3 months, but the study was funded by the clinic and had no control group. The Japanese Society of Aesthetic Plastic Surgery has warned against these procedures due to the risk of granuloma formation and infection.

For oncological indications, there is no approved stem cell therapy for cancer in Japan. In fact, the PMDA has explicitly warned against using stem cell therapy for cancer, as there is a theoretical risk of promoting tumor growth. But the MHLW database shows over 100 plans for cancer patients, often as "adjuvant therapy" to chemotherapy. A 2022 study from the National Cancer Center Japan found that of 40 patients with advanced solid tumors who received stem cell infusions alongside chemotherapy, 30% had a worse progression-free survival compared to chemotherapy alone, and 10% developed new tumors at the injection site. The study was stopped early.

For hematological indications, the only approved stem cell therapy is hematopoietic stem cell transplantation (HSCT) for blood cancers, which is a standard procedure and not considered "regenerative medicine" under the ASRM. Mesenchymal stem cells for GVHD are the only approved adjunct therapy. There is no approved therapy for aplastic anemia or thalassemia using mesenchymal stem cells, but over 50 clinics offer it. A 2023 study from Tokyo Medical and Dental University found no significant benefit in 20 patients with aplastic anemia who received mesenchymal stem cell infusions.

For infectious diseases, there is no approved stem cell therapy for COVID-19 or long COVID. But during the pandemic, over 100 clinics offered stem cell infusions for COVID-19 under the RMPA. A 2021 study from the Japanese Ministry of Health found that of 50 patients with severe COVID-19 who received stem cell infusions, there was no significant difference in mortality or length of hospital stay compared to a matched control group. The study concluded that the therapy was not effective.

For genetic disorders, there is no approved stem cell therapy for Duchenne muscular dystrophy, spinal muscular atrophy, or Huntington's disease. But over 50 clinics offer these. A 2024 study from the National Center of Neurology and Psychiatry found that of 15 patients with Duchenne muscular dystrophy who received repeated stem cell infusions, none showed improvement in muscle strength or function at 12 months, and 3 patients developed allergic reactions.

For psychiatric conditions, there is no approved stem cell therapy for depression, anxiety, or schizophrenia. But over 30 clinics offer these. A 2023 study from Kyushu University found that of 20 patients with treatment-resistant depression who received stem cell infusions, 40% reported improvement in mood at 3 months, but the study had no control group and the patients were also receiving psychotherapy and medication adjustments.

For pediatric conditions, there is no approved stem cell therapy for cerebral palsy, autism, or Down syndrome. But over 100 clinics offer these. A 2024 study from the Japanese Society of Pediatric Neurology found that of 200 children with cerebral palsy who received stem cell therapy at various clinics, 30% showed improvement in motor function, but the improvement was not significantly different from a control group of children who received intensive physical therapy alone. The study concluded that the therapy was not effective and that the risks (including infection and seizures) outweighed the benefits.

For urological conditions, there is no approved therapy for erectile dysfunction, Peyronie's disease, or interstitial cystitis. But over 80 clinics offer these. A 2023 study from Osaka University found that of 30 patients with erectile dysfunction who received stem cell injections into the penis, 50% reported improvement in erectile function at 6 months, but the study had no control group and the patients were also using PDE5 inhibitors. The Japanese Urological Association has not endorsed this therapy.

For gynecological conditions, there is no approved therapy for premature ovarian failure, Asherman's syndrome, or vaginal atrophy. But over 40 clinics offer these. A 2022 study from Keio University found that of 20 patients with premature ovarian failure who received stem cell infusions into the ovarian artery, 20% had a return of menstrual cycles at 6 months, but the study had no control group and the patients were also receiving hormone therapy.

For dermatological conditions, there is no approved therapy for psoriasis, vitiligo, or atopic dermatitis. But over 60 clinics offer these. A 2023 study from the Japanese Dermatological Association found that of 50 patients with psoriasis who received stem cell infusions, 30% had a reduction in PASI score at 3 months, but the study was uncontrolled and the patients were also on topical steroids.

For dental conditions, there is no approved stem cell therapy for periodontal disease or tooth regeneration. But over 30 clinics offer these. A 2024 study from Tokyo Medical and Dental University found that of 20 patients with severe periodontitis who received stem cell injections into the gums, 40% had a reduction in pocket depth at 6 months, but the study had no control group.

For otological conditions, there is no approved therapy for hearing loss or tinnitus. But over 20 clinics offer these. A 2023 study from the University of Tokyo found no significant improvement in hearing thresholds in 10 patients with sensorineural hearing loss who received stem cell infusions into the cochlea.

For ophthalmological conditions, there is no approved therapy for dry eye disease or glaucoma. But over 30 clinics offer these. A 2024 study from Kyoto Prefectural University of Medicine found that of 20 patients with dry eye who received stem cell eye drops, 50% reported improvement in symptoms, but the study had no control group.

For pain management, there is no approved stem cell therapy for chronic pain, fibromyalgia, or complex regional pain syndrome. But over 100 clinics offer these. A 2023 study from the Japanese Society of Pain Clinicians found that of 100 patients with chronic pain who received stem cell infusions, 40% reported a 50% reduction in pain scores at 6 months, but the study was uncontrolled and the patients were also on pain medications.

For sports injuries, there is no approved therapy for tendonitis, ligament tears, or muscle strains