Muse Cells: Stress-Resistant, Pluripotent Stem Cells from Adult Tissues

Multilineage-differentiating Stress-Enduring or Muse cells are a rare subset (~1%) of mesenchymal stem cells identified by the marker SSEA-3, found across various adult tissues including bone marrow, adipose tissue, skin, umbilical cord, and even peripheral blood.

Key Characteristics:

• Pluripotent-like, yet Non-tumorigenic: Unlike embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), Muse cells can differentiate into cell types across all three germ layers—including neural, hepatic, cardiac, and epidermal lineages, without forming teratomas when transplanted in vivo.

• Stress-Enduring & Immune-Modulating: Muse cells are uniquely resilient, capable of surviving harsh conditions and secreting protective proteins like serpins and 14-3-3 proteins, which provide anti-apoptotic and anti-inflammatory effects. They also express high levels of HLA‑G, which aids immune evasion, making them promising for allogeneic use.

• Efficient Isolation & Use: Isolation protocols are streamlined, cells are sorted using SSEA‑3, expanded in vitro, and then ready for transplantation, bypassing the complex reprogramming required for ESCs or iPSCs

Therapeutic Applications: Preclinical to Early Clinical

Research across models and preliminary clinical studies shows Muse cells have broad regenerative potential:

• Stroke and Brain Injury: In murine stroke models, Muse cells homed to the injury site, differentiated into neuronal cells, and improved functional recovery—especially when delivered via nose-to-brain routes.

• Neuropathic Pain: In a 2025 preprint, Muse cells alleviated neuropathic pain in mouse models through intrathecal delivery, modulating inflammation via secretion of TGF-β and IL-10.

• Radiation-Induced Injury: Preclinical work suggests Muse cells derived from bone marrow may help repair intestinal damage caused by radiation.

• Neurodegenerative Disease (ALS): Early-phase clinical trials in ALS patients using allogeneic Muse cells showed safety and tolerability, with most patients exhibiting stable function over 10 months—even without immunosuppression.

Overall, Muse cells combine homing ability, spontaneous differentiation at damage sites, and immune privilege, making them an exciting tool for regenerative and cell-free therapies.

References

1. Wikipedia – Muse cell overview and pluripotent non-tumorigenicity wired.com+14Wikipedia+14Stem Cell Regeneration Center+14BioMed Central+2BioMed Central+2PMC+2journals.lww.com+2

2. Muse cell biology, immunomodulation, and isolation benefits BioMed Central

3. Nose-to-brain delivery of Muse cells in cerebral infarct models journals.lww.com+10Nature+10Wikipedia+10

4. Muse cells in neuropathic pain via TGF-β and IL-10 pathways arXiv

5. Preclinical radiation injury repair using Muse cells advancesradonc.com

6. ALS clinical potential and safety profile of Muse cell treatment Frontiers