Muse cells as a robust source of induced pluripotent stem cells

Abstract Multilineage-differentiating stress enduring (Muse) cells are present in the bone marrow, peripheral blood, and organ connective tissue as cells positive for the pluripotent cell surface marker stage specific embryonic antigen-3. Muse cells exhibit pluripotent-like characteristics represented by the expression of pluripotency markers, as well as triploblastic differentiation and self-renewal at the single-cell level. They show unique tissue reparative functions in vivo: selective migration to the site of damage mediated by the sphingosine-1-phosphate (S1P)–S1P receptor 2 axis; spontaneous differentiation into multiple cell types comprising the tissue; and tissue repair. Muse cells comprise several percent of the total population of fibroblasts. When fibroblasts are separated into Muse cells and the remaining cells, namely non-Muse fibroblasts, and each fraction is subjected to induce pluripotent stem cell (iPSC) generation, only Muse cells, and not non-Muse cell fibroblasts, generate iPSCs. Thus, Muse cells could be a robust candidate source for the efficient generation of iPSCs.