Muse Cells Guide | Akira Biotech

Overview

Multilineage-differentiating stress-enduring (Muse) cells are a rare subpopulation found within mesenchymal tissues and cultured mesenchymal stem cells. They were first reported in 2010 by Mari Dezawa's group at Tohoku University, who isolated them from human bone marrow aspirates, mesenchymal cultures, and dermal fibroblasts on the basis of their resistance to cellular stress.^[1] Muse cells are identified by surface expression of SSEA-3 — a marker classically associated with embryonic stem cells — together with mesenchymal markers such as CD105, and they behave as a pluripotent-like population while remaining non-tumorigenic.^[2]

Related: Stem Cells Overview · Wharton's Jelly

FOR RESEARCH USE AND INTERNATIONAL USE ONLY

Specs	Details
Cell Type	Muse cells — SSEA-3+ / CD105+ stress-enduring subpopulation of the mesenchymal compartment^[1]
Source Tissue	Umbilical cord tissue (Wharton's Jelly)^[3]
Identity Markers	SSEA-3, CD105, CD90, CD73, CD29, CD44; CD45 negative^[3]
Pluripotency Markers	Nanog, Oct3/4, Sox2 expressed without genetic manipulation^[2]
Enrichment	SSEA-3 selection (flow cytometry or magnetic-activated cell sorting)^[3]
Formats	Cryopreserved cell suspension
Storage	−80 °C long-term; −196 °C LN2 vapor phase for extended phase
Immunogenicity	Allogeneic use reported without HLA matching or immunosuppression in published clinical studies^[4]
Manufacturing	cGMP, animal-product-free

Muse cells are not a separate lineage of the body but a minority population that coexists with ordinary mesenchymal stromal cells. In adherent culture they are indistinguishable from other MSCs by morphology; it is surface SSEA-3 expression, and their behavior in suspension culture, that sets them apart.^[1] Akira's Muse Cells sit alongside — rather than replace — the mesenchymal stem cell product: MSCs are the broad, immunomodulatory, paracrine workhorse, while Muse cells are a selected, pluripotent-like fraction studied for direct tissue integration.

Biology

What Makes Muse Cells Distinct

Stress endurance. Muse cells were originally enriched by subjecting mesenchymal cultures and bone marrow aspirates to severe cellular stress — notably long-term trypsin incubation — which most cells do not survive. The survivors are enriched in the SSEA-3-positive fraction.^[1]^[2]

Cluster formation. In single-cell suspension culture, Muse cells form characteristic embryoid-body-like clusters that express pluripotency markers. When these clusters are transferred to adherent culture, they spontaneously give rise to cells representative of ectoderm, mesoderm, and endoderm, and single Muse cells can be re-cloned, demonstrating self-renewal.^[1]^[2]

Non-tumorigenicity. Unlike embryonic stem cells and induced pluripotent stem cells, Muse cells have low telomerase activity, a normal karyotype, and do not form teratomas when transplanted into immunodeficient mice.^[2] This is the property most often highlighted as separating them from other pluripotent populations.

Abundance. Muse cells are a small fraction of any source. Published estimates place SSEA-3-positive cells at roughly 0.03% to several percent of cultured mesenchymal populations such as bone marrow, adipose tissue, and dermal fibroblasts.^[3] In freshly processed umbilical cord, SSEA-3-positive cells have been measured at about 5% of Wharton's Jelly cells at passage 0, declining over subsequent passages unless they are re-enriched.^[3]

Umbilical cord as a source. Fetal-stage tissue such as the umbilical cord is a rich source of Muse cells: magnetic sorting of cord-derived cells yielded cultures of roughly 90% SSEA-3-positive cells, which could be maintained and re-sorted through extended passaging.^[3] Muse cells isolated from human umbilical cord have also been described as sharing gene-expression, DNA methylation, and differentiation features with post-implantation-stage embryonic cells.^[5]

Mechanism

Proposed Mechanism of Action

Research on Muse cells centers on a sequence that differs from the paracrine-only model usually applied to mesenchymal stem cells:

Damage sensing and homing. Damaged tissue releases sphingosine-1-phosphate (S1P). Muse cells express high levels of the S1P receptor S1PR2 and have been reported to home selectively to injured tissue after systemic administration in animal models, including acute myocardial infarction.^[6]

Engraftment and spontaneous differentiation. After homing, Muse cells integrate into the damaged tissue and differentiate into cells matching the local microenvironment — for example cardiomyocytes and vascular cells in infarcted heart in preclinical work — rather than relying solely on secreted factors.^[7]^[8]

Immune tolerance. Muse cells express HLA-G, a molecule central to maternal–fetal tolerance, and produce indoleamine 2,3-dioxygenase, TGF-β, PGE2, nitric oxide, and HGF. This profile is proposed to explain why donor Muse cells have been administered in clinical studies without HLA matching or immunosuppressants.^[4]

Stress tolerance in damaged tissue. The same stress resistance that defines the population in culture is thought to help Muse cells survive the hostile ischemic, inflamed environment of injured tissue.^[7]

These mechanisms are drawn from published preclinical and early clinical research, largely on bone-marrow-derived and other Muse preparations. They are investigational, and their relevance to any specific product lot should be established by the researcher.

Comparison

Muse Cells vs. Conventional MSCs

Feature	Muse Cells	Conventional MSCs
Population	Rare SSEA-3+ subpopulation	Heterogeneous bulk population
Pluripotency markers	Nanog, Oct3/4, Sox2, SSEA-3^[2]	Generally absent
Differentiation	All three germ layers^[1]	Primarily mesodermal (bone, cartilage, fat)
Tumorigenicity	Non-tumorigenic; low telomerase^[2]	Non-tumorigenic
Principal research framing	Homing, engraftment, differentiation	Paracrine and immunomodulatory signaling
Abundance	~0.03% to several percent of a culture^[3]	Majority of culture

Muse cells and MSCs are complementary research tools. Comparing them in the same model — with the Wharton's Jelly MSC product as the bulk-population control — is one way to separate engraftment-driven effects from paracrine effects.

Applications

Potential Research Applications

Muse cells are studied in models where tissue loss or ischemic damage is central and where a cell that can both home to injury and replace lost cell types is of interest:

Ischemic cardiovascular injury — homing, engraftment, and cardiomyocyte differentiation after myocardial infarction models^[6]
Ischemic and neurodegenerative neural injury — stroke, spinal cord injury, and neurodegeneration models^[7]
Neonatal hypoxic-ischemic brain injury — safety and exploratory outcomes in neonates undergoing therapeutic hypothermia^[9]
Skin and connective tissue disorders — chronic ulcer models, including dystrophic epidermolysis bullosa^[10]
Liver, kidney, and lung injury models — tissue-specific homing and differentiation studies^[7]
Comparative stem cell biology — pluripotent-like but non-tumorigenic behavior as a benchmark against ES cells, iPS cells, and bulk MSCs^[2]

All Akira products are supplied for research use only.

These are experimental use cases, provided as a scientific reference for researchers. Except where noted, they did not use Akira Biotech materials, and results may not be reproducible with ours. Akira Biotech supplies laboratory reagents for research use only. Our products are NOT approved by FDA or any regulatory authority and are not for use in or on humans.

Evidence

Clinical & Preclinical Evidence

Clinical work on Muse cells to date has been conducted in Japan with CL2020, an allogeneic Muse cell-based product. The studies below are small, largely open-label, early-phase investigations; none establishes efficacy for any condition, and none involved Akira's product.^[4]

Study / Trial	N / Design	Endpoints	Reported Outcome
Acute myocardial infarction, first-in-human^[11]	3 STEMI patients with LVEF ≤45% after PCI; single IV dose of 1.5×10⁷ cells; 12-week follow-up	Safety, LVEF	No cell-therapy-associated safety concerns reported; LVEF rose from 40.7% to 52.0% over 12 weeks^[4]
Subacute ischemic stroke, Phase 2^[4]	35 patients randomized 25 CL2020 : 10 placebo; single IV dose 14–28 days post-stroke; 52-week follow-up	Safety; response rate (mRS ≤2 at 12 weeks)	40% response in the CL2020 group vs. 10% with placebo; no serious adverse reactions attributed to rejection without immunosuppression
Dystrophic epidermolysis bullosa, Phase 1/2^[10]	5 adults with refractory ulcers; single IV dose of 1.5×10⁷ cells; 52-week follow-up	Safety, ulcer size	2 of 5 patients showed >50% reduction in a selected ulcer at 4 weeks; no serious adverse reactions attributed to the cells reported^[4]
Neonatal HIE, SHIELD trial^[9]	9 neonates on therapeutic hypothermia; 3+3 dose escalation (1.5×10⁶ and 1.5×10⁷ cells)	Adverse events within 12 weeks	No serious adverse events related to administration; all 9 survived; 67% had normal developmental quotients at 78 weeks
Sporadic ALS^[4]	5 patients; monthly IV dosing for 6 months; 12-month follow-up	Safety, ALSFRS-R	ALSFRS-R scores remained stable in 4 of 5 patients

Preclinical literature adds S1P–S1PR2-mediated homing to infarcted myocardium and spontaneous differentiation into cardiomyocytes and vascular cells,^[6] alongside rodent work in stroke, spinal cord, liver, kidney, and neurodegeneration models summarized in recent reviews.^[7]^[8]

Limitations. Most trials are very small, open-label, or lack a randomized control; several endpoints are exploratory. Muse cell isolation is also method-dependent, and published results come from specific preparations that may not generalize to other sources or protocols. Researchers should treat these findings as hypothesis-generating.

Muse Cells