Macrophage-like and pluripotent-like reparative Muse cells are unique endogenous stem cells distinct from other somatic stem cells

Mari Dezawa ^*

• School of Medicine, Tohoku University, Sendai, Japan

Muse cells are endogenous reparative stem cells with dual aspects of pluripotent-like and macrophage-like that can be identified as pluripotent surface marker SSEA-3(+) cells in the bone marrow, peripheral blood, and various organs, including umbilical cord and amnion. They can differentiate into ectodermal-, endodermal-, and mesodermal-lineage cells and self-renew, selectively migrate to damaged sites by sensing one of the universal tissue damage signals, sphingosine-1-phosphate(S1P), where they phagocytose damaged/apoptotic cells and differentiate into the same cell type as the phagocytosed cells. In this manner, Muse cells replace damaged/apoptotic cells with healthy functioning cells and repair tissues. Due to their specific immunosuppressive and immunotolerant mechanism, clinical trials for acute myocardial infarction, subacute ischemic stroke, epidermolysis bullosa, amyotrophic lateral sclerosis, cervical spinal cord injury, neonatal hypoxic-ischemic encephalopathy, and COVID19 acute respiratory distress syndrome were all conducted by intravenous injection of ~1.5x107 donor Muse cells without HLA-matching test or immunosuppressant treatment, and safely and therapeutic efficacy were reported. Thus, donor Muse cell treatment does not require gene manipulations, differentiation inductions, or surgical intervention. These unique characteristics distinguish Muse cells from other somatic stem cells, such as mesenchymal stem cells, VSELs, and MIAMI cells.