Published preclinical and Phase II clinical data report a favorable safety profile for Dezawa Muse cells. No teratoma formation has been documented in any animal or human study. Serious adverse events in published trials have been rare, and in most cases investigators determined no causal connection to the cells themselves. Dezawa Muse cells have not been evaluated or approved by the U.S. Food and Drug Administration. The clinical evidence base remains early-stage, trial populations are small, and no large randomized placebo-controlled studies with long-term follow-up have been published yet. Individual outcomes vary.
Why the safety question deserves a serious answer
When patients research Dezawa Muse cell therapy, "is this safe?" is nearly always the first question. The stem cell field has a credibility problem - years of overpromising from poorly regulated clinics has made people appropriately skeptical of any cell-based product. That skepticism is warranted, and it deserves a data-grounded response rather than reassurance.
This article pulls from peer-reviewed publications, registered clinical trial results, and published preclinical data. Every safety claim here is tied to a specific citation. Where the data is strong, that is noted. Where it is limited, that is noted too. The goal is an accurate picture, not a promotional one.
For context on what Dezawa Muse cells are and how they work before reading about their safety, see What Are Dezawa Muse Cells? and How Do Dezawa Muse Cells Work?
The tumor question: can Muse cells form teratomas?
Tumor formation is the primary safety concern with any pluripotent stem cell. Pluripotent cells - cells that can become any tissue type - carry the biological potential to form teratomas, a specific type of tumor containing a disorganized mix of tissue from multiple germ layers. Both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) reliably produce teratomas in the standard preclinical test: injection into immunodeficient mice, the most sensitive model for detecting this risk.
Dezawa Muse cells are also pluripotent. The reasonable concern is that they would carry the same risk.
Published data, across multiple independent laboratories, says otherwise. No teratoma formation has been observed in any published preclinical study of Dezawa Muse cells, including long-term implantation in immunodeficient mice over six months. This result has been replicated, not just reported once.
Why don't Muse cells form teratomas?
The answer lies in a molecular regulatory system called the Let-7/Lin28 axis. In ESCs and iPSCs, a protein called Lin28 is highly active. Lin28 blocks the maturation of Let-7 microRNA, a known tumor suppressor. With Let-7 suppressed, cells proliferate rapidly and without restraint - which is what produces tumors.
In Dezawa Muse cells, Lin28 is not expressed at all. Let-7 is elevated to levels higher than in iPSCs. A 2023 study published in Cellular and Molecular Life Sciences confirmed that in Muse cells, Let-7 inhibits the PI3K-AKT signaling pathway - a key regulator of cell growth and proliferation - which suppresses uncontrolled division while still maintaining pluripotency markers like KLF4, POU5F1 (Oct3/4), SOX2, and NANOG.
In plain language: Muse cells maintain their ability to become different tissue types through a different molecular route than ESCs or iPSCs, and that route does not carry the same tumor risk profile.
Two additional markers reinforce this:
- Low telomerase activity. Telomerase is an enzyme that extends chromosomal telomeres, effectively giving cells the ability to divide indefinitely. High telomerase activity is associated with cancer. Muse cells have intrinsically low telomerase activity, which limits their capacity for uncontrolled proliferation.
- Stable karyotype. Published manufacturing data confirms that Muse cells maintain a normal, intact chromosome count across extended cell culture. Chromosomal instability - which can emerge in some stem cell preparations during repeated division - has not been observed in published Muse cell studies.
The immune privilege advantage: why no immunosuppressants are needed
One of the most clinically significant safety differences between Dezawa Muse cells and other cell-based therapies is that they do not require immunosuppressive medication. Immunosuppressive drugs - medications that suppress the immune system to prevent rejection of foreign cells or organs - carry their own serious risks: increased infection susceptibility, organ toxicity, and elevated long-term cancer risk. Avoiding them is a meaningful safety advantage.
In every published clinical trial, allogeneic (donor-derived) Dezawa Muse cells were administered without immunosuppressants, and immune rejection was not observed.
The biological explanation is their surface protein profile. Dezawa Muse cells express:
- HLA-G at levels 5 to 7 times higher than regular mesenchymal stem cells. HLA-G was first identified in the placenta, where it protects the developing fetus from maternal immune rejection. It strongly suppresses the proliferation and activity of T cells, B cells, natural killer cells, macrophages, dendritic cells, and neutrophils.
- Indoleamine 2,3-dioxygenase (IDO), an enzyme that suppresses immune responses through tryptophan metabolism and supports regulatory T-cell activation.
- HLA-A, -B, and -C (standard immune identity markers), but not HLA-DR (the major histocompatibility class II molecule that triggers the strongest immune rejection responses).
A 2024 study published in Nature Communications Medicine demonstrated that intravenously administered human Muse cells could reconstruct aortic tissue in mouse models without immunosuppression. In kidney injury models, human Muse cells survived in host glomerular tissue for nearly two months without immunosuppressants, while non-Muse mesenchymal stem cells became undetectable within two weeks.
Published research in PubMed describes this as "endogenous reparative pluripotent Muse cells with a unique immune privilege system" - noting that the full mechanism has not yet been fully characterized, but the clinical outcome (no immunosuppression required, no observed rejection) has been consistent across published trials.
What the clinical trials actually show
Multiple registered clinical trials have evaluated Dezawa Muse cells in human patients across different conditions. Here is the published safety record.
Acute myocardial infarction (heart attack) - first-in-human study
The first published human study administered intravenous CL2020 (the tradename for the licensed Muse cell product developed by Life Science Institute, a subsidiary of Mitsubishi Chemical Group) to 3 patients with ST-elevation myocardial infarction and reduced heart function. Over 12 weeks of evaluation, no adverse drug reactions were reported. Left ventricular function improved measurably in all three patients. This was a small first-in-human safety study, not a definitive efficacy trial, but the zero adverse reaction rate at this stage was a necessary condition for advancing to larger trials.
ALS (Amyotrophic Lateral Sclerosis) - Phase II trial (jRCT2063200047)
Five patients with sporadic ALS received six monthly intravenous doses of CL2020. Over 12 months of follow-up, 28 adverse events occurred across the five patients. The most common were headache (4 cases) and fatigue (3 cases). Other reported events included nausea, fever, back pain, and eczema - most consistent with general illness rather than cell-specific toxicity.
One serious adverse event occurred: a bone fracture in one patient at 12 months. After investigation, the study authors ruled out any causal link between the fracture and CL2020 treatment. No pulmonary embolisms, no anaphylactic reactions, no tumor-related events, and no significant changes in vital signs, laboratory values, or electrocardiogram readings were observed across the cohort.
Ischemic stroke - randomized placebo-controlled trial (jRCT2043200047)
This is the most rigorous published Muse cell trial to date. Twenty-five patients received CL2020 and 10 received placebo, without immunosuppression, in a randomized, double-blind design. By week 12, 96% of the CL2020 group had experienced some adverse event, compared to 100% in the placebo group - a rate consistent with a medically complex stroke recovery population rather than a cell-specific signal.
One serious adverse reaction was attributed to CL2020: Grade 4 status epilepticus in a 56-year-old patient, occurring 86 days after treatment. The patient recovered with antiepileptic medication. The authors classified this as a serious adverse reaction, not merely an adverse event. It is worth noting clearly because transparency about serious events is part of what distinguishes responsible clinical reporting.
An unexpected finding was hair darkening - 24% of CL2020 patients developed dark hair pigmentation where their hair had previously been gray or white, compared to none in the placebo group. The mechanism is not established, but it suggests systemic activity of the cells beyond the target tissue. No adverse health consequences from this observation were reported.
Neonatal hypoxic-ischemic encephalopathy - SHIELD trial (NCT04261335)
Nine newborns with brain injury from oxygen deprivation at birth were enrolled. Three received a low dose and six received a higher dose of CL2020, administered alongside standard hypothermia therapy. Follow-up extended to 78 weeks. Across that period, 102 adverse events were recorded across 9 patients - most in the categories of skin/subcutaneous disorders, infections, and gastrointestinal events consistent with neonatal illness generally.
One serious adverse event occurred: a respiratory syncytial virus (RSV) infection, which was determined to be unrelated to cell administration. One potentially treatment-related event was a mild elevation of a liver enzyme (gamma-glutamyltransferase) that resolved on its own without intervention. The study authors concluded that "CL2020 administration was demonstrated to be safe and tolerable for neonates with HIE."
Spinal cord injury - safety and feasibility study
A clinical trial evaluating intravenous Muse cells for cervical traumatic spinal cord injury was published in 2024 in Stem Cell Research and Therapy. The study confirmed feasibility of IV administration and reported no IV-specific complications - no pulmonary embolism, no anaphylaxis, no cell-related serious adverse events.
How this compares to other stem cell approaches
Understanding what makes Dezawa Muse cells different requires comparing their safety profile to the two most common stem cell categories patients encounter.
| Safety factor | ESCs / iPSCs | Mesenchymal stem cells | Dezawa Muse cells |
|---|---|---|---|
| Teratoma formation | Yes - observed in preclinical models | Not observed | Not observed |
| Immunosuppressants required | Yes (for allogeneic use) | Variable - some protocols require them | Not required in published trials |
| Stable karyotype in culture | Variable - can develop instability | Generally stable short-term | Documented across extended culture |
| Telomerase activity | High | Low to moderate | Low |
| Genetic modification required | iPSCs require gene reprogramming | No | No |
| FDA approval status | No approved clinical applications | Limited approved applications | Not FDA approved |
The comparison to regular mesenchymal stem cells (MSCs) deserves a more careful look. MSCs have a substantial clinical trial record - far larger than the current Muse cell dataset - and their safety profile is also favorable. The meaningful distinction is not that Muse cells are safer than MSCs. It is that Muse cells appear to maintain safety while also being pluripotent, which MSCs are not. Pluripotency, in theory, means Muse cells have broader tissue-regeneration capacity. Whether that theoretical advantage translates to superior clinical outcomes will require larger trials.
What the current evidence cannot tell us
A fair assessment of the Dezawa Muse cell safety record requires acknowledging what it does not yet include:
- Large-scale randomized controlled trials. The largest published trial enrolled 35 patients total (25 treatment, 10 placebo). That is a meaningful start, but standard safety thresholds in drug development typically require hundreds to thousands of patients before rare adverse events can be reliably detected.
- Long-term follow-up beyond 78 weeks. The longest published follow-up is 78 weeks from the SHIELD neonatal trial. Decade-scale safety data does not yet exist for clinical populations.
- Diverse patient populations. Published trials have been conducted primarily in Japan. Immunological and genomic factors can vary across populations, and those differences have not been fully studied.
- Direct comparison to placebo across all conditions. Only the ischemic stroke trial used a placebo-controlled design. Interpreting adverse event rates in uncontrolled trials requires caution because many events reflect the underlying illness rather than the treatment.
These limitations do not negate the positive safety signals. They define the boundaries of what those signals can currently support. The evidence base for Dezawa Muse cells is genuinely promising and more mechanistically grounded than most stem cell therapies at a comparable stage. It is also still developing.
Dr. Capasso's perspective on these findings
When I evaluated whether to offer Dezawa Muse cell therapy at Regener8MD, the safety profile was the deciding factor - not the efficacy data, not the commercial opportunity. My standard was simple: would I use this for someone I care about?
The combination of no teratoma formation across any published model, no immune rejection without immunosuppressants, stable chromosome integrity, and low telomerase activity gives Dezawa Muse cells a preclinical safety profile unlike any other pluripotent cell type I have reviewed. The clinical trial record - while small - has been consistent with that preclinical profile.
What I tell patients directly: the evidence is favorable, the mechanism makes biological sense, and the risks documented to date are manageable. It is also early-stage science. There are unknowns that future trials will resolve. My role is to give you an accurate picture of what is known, what is not, and where your individual health situation fits within that picture.
That conversation happens at your consultation. It cannot happen in a blog post.
Key citations and sources
- Yamashita T, Nakano Y, Sasaki R, et al. (2023). Safety and Clinical Effects of a Muse Cell-Based Product in Patients With Amyotrophic Lateral Sclerosis: Results of a Phase 2 Clinical Trial. Cell Transplantation. jRCT2063200047. PMC10686030.
- Niizuma K, Osawa S, Endo H, et al. (2023). Randomized placebo-controlled trial of CL2020, an allogenic Muse cell-based product, in subacute ischemic stroke. Journal of Cerebral Blood Flow and Metabolism. jRCT2043200047. PMID 37756573.
- Miura Y, et al. (2024). Safety and tolerability of a Muse cell-based product in neonatal hypoxic-ischemic encephalopathy with therapeutic hypothermia (SHIELD trial). Stem Cells Translational Medicine, 13(11):1053. NCT04261335. PMC11555474.
- Abe K, et al. (2020). Safety and Efficacy of Human Muse Cell-Based Product for Acute Myocardial Infarction in a First-in-Human Trial. Circulation Journal. PMID 32522904.
- Wakao S, et al. (2023). Tumor suppressor let-7 acts as a key regulator for pluripotency gene expression in Muse cells. Cellular and Molecular Life Sciences. doi:10.1007/s00018-023-05089-9.
- Dezawa M, et al. (2023). Endogenous reparative pluripotent Muse cells with a unique immune privilege system: Hint at a new strategy for controlling acute and chronic inflammation. PubMed. PMID 36339573.
- Wakao S, Dezawa M. (2024). Donor Muse Cell Treatment Without HLA-Matching Tests and Immunosuppressant Treatment. Stem Cells Translational Medicine, 13(6):532. doi:10.1093/stcltm/szae024.
- Kuroda Y, Kitada M, Wakao S, et al. (2010). Unique multipotent cells in adult human mesenchymal cell populations. Proceedings of the National Academy of Sciences, 107(19):8639-8643.
Frequently asked questions
Are Dezawa Muse cells safe?
Published preclinical and Phase II clinical data report a favorable safety profile. No teratoma formation has been observed in any preclinical or clinical study. Serious adverse events in clinical trials have been rare, and in most cases investigators determined no causal link to the cells themselves. Dezawa Muse cell therapy has not been evaluated or approved by the U.S. FDA, and individual outcomes vary.
Can Muse cells form tumors?
No teratoma formation has been observed in published preclinical studies, including long-term implantation in immunodeficient mice. This distinguishes Muse cells from embryonic stem cells and iPSCs, both of which form teratomas in the same animal models. The safety advantage is linked to elevated Let-7 microRNA and the absence of Lin28 expression, a molecular profile that actively suppresses uncontrolled cell division.
Do Muse cells require immunosuppressants?
No. In every published clinical trial, allogeneic (donor-derived) Muse cells were administered without immunosuppressive medication, and immune rejection was not reported. This is attributed to the cells' expression of HLA-G at levels 5 to 7 times higher than regular mesenchymal stem cells, along with IDO activity and the absence of HLA-DR on the cell surface.
Have there been serious adverse events in Muse cell trials?
Yes. In the ALS Phase II trial, one patient experienced a bone fracture, which was ruled unrelated to treatment. In the ischemic stroke placebo-controlled trial, one patient experienced Grade 4 status epilepticus that was classified as a serious adverse reaction to CL2020. In the SHIELD neonatal trial, one infant had a respiratory virus infection unrelated to treatment. No tumor-related, pulmonary embolism, or anaphylaxis events have been reported across the published trial record.
What does stable karyotype mean for Muse cells?
Karyotype refers to the complete set of chromosomes in a cell. A stable karyotype means chromosomes remain structurally intact and correctly numbered even after the cells have been cultured and multiplied in a laboratory. Chromosomal instability in some stem cell preparations can introduce errors that raise cancer risk. Published research has documented that Dezawa Muse cells maintain a stable karyotype across extended culture, which is one of the quality markers used to verify batches before clinical use.
Is IV infusion of Muse cells safe?
Intravenous administration is the primary route used in published trials. No IV-specific complications such as pulmonary embolism or anaphylactic shock have been reported across the published trial population. The cells' homing mechanism via the S1P-S1PR2 receptor system is thought to direct them toward injured tissue, which may explain the absence of the lung-trapping effect seen with regular mesenchymal stem cells. The total clinical population receiving IV Muse cells is still small, and ongoing monitoring is warranted.
How is Muse cell safety different from embryonic stem cells?
Embryonic stem cells and iPSCs reliably form teratomas when injected as undifferentiated cells in immunodeficient mouse models. This tumor risk has prevented their direct clinical use. Dezawa Muse cells are pluripotent but have not formed teratomas in the same models. The key difference is the Let-7/Lin28 molecular axis: Lin28 is absent in Muse cells, and Let-7 is elevated, suppressing the growth signaling pathway that would otherwise drive tumor formation.
Are Dezawa Muse cells FDA approved?
No. Dezawa Muse cell therapy has not been evaluated or approved by the U.S. Food and Drug Administration for any indication. The product CL2020 has advanced through Phase II clinical trials in Japan under the Japan Registry of Clinical Trials. Clinical use in the United States takes place under physician discretion within applicable regulatory frameworks. This does not constitute FDA approval.
Want to know if this is appropriate for your situation?
Dr. Capasso offers a complimentary consultation to review your health history, walk through the published evidence, and give you a direct assessment of whether regenerative therapies are a reasonable fit for your goals.
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