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Muse cells can differentiate into ectodermal, endodermal, and mesodermal lineage cells, self-renew, and selectively migrate to damaged sites by sensing one of the universal tissue damage signals, sphingosine-1-phosphate (S1P). At these sites, 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, thereby repairing tissues. Due to their specific immunosuppressive and immunotolerant mechanism, clinical trials have been conducted for acute myocardial infarction (AMI), subacute ischemic stroke, epidermolysis bullosa, amyotrophic lateral sclerosis (ALS), cervical spinal cord injury, neonatal hypoxic-ischemic encephalopathy (HIE), and COVID-19 acute respiratory distress syndrome. These trials involved the intravenous injection of \u223c1.5 \u00d7 10<jats:sup>7<\/jats:sup> donor Muse cells without human leukocyte antigen (HLA) matching or immunosuppressant treatment, and they demonstrated safety and therapeutic efficacy. Thus, donor Muse cell treatment does not require gene manipulation, differentiation induction, or surgical intervention. These unique characteristics distinguish Muse cells from other somatic stem cells, such as mesenchymal stem cells, VSEL stem cells, and marrow-isolated adult multi-lineage inducible (MIAMI) cells.<\/jats:p>","DOI":"10.3389\/fbioe.2025.1553382","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T01:51:04Z","timestamp":1743126664000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Macrophage- and pluripotent-like reparative Muse cells are unique endogenous stem cells distinct from other somatic stem cells"],"prefix":"10.3389","volume":"13","author":[{"given":"Mari","family":"Dezawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1161\/strokeaha.119.026589","article-title":"Intravenously transplanted human multilineage-differentiating stress-enduring cells afford brain repair in a mouse lacunar stroke model","volume":"51","author":"Abe","year":"2020","journal-title":"Stroke"},{"key":"B2","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1080\/15384101.2016.1211215","article-title":"The secretome of MUSE cells contains factors that may play a role in regulation of stemness, apoptosis and immunomodulation","volume":"16","author":"Alessio","year":"2017","journal-title":"Cell Cycle"},{"key":"B3","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1177\/0963689717721514","article-title":"Cardiotrophic growth factor-driven induction of human muse cells into cardiomyocyte-like phenotype","volume":"27","author":"Amin","year":"2018","journal-title":"Cell Transpl."},{"key":"B4","doi-asserted-by":"publisher","first-page":"761","DOI":"10.3390\/cells10040761","article-title":"MUSE stem cells can Be isolated from stromal compartment of mouse bone marrow, adipose tissue, and ear connective tissue: a comparative study of their in vitro properties","volume":"10","author":"Aprile","year":"2021","journal-title":"Cells"},{"key":"B5","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1186\/s13287-024-03752-x","article-title":"Multipotent\/pluripotent stem cell populations in stromal tissues and peripheral blood: exploring diversity, potential, and therapeutic applications","volume":"15","author":"Aprile","year":"2024","journal-title":"Stem Cell Res. 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