Muse cells: a novel type of adult human pluripotent stem cells and their possible application to cell therapy

We found a unique type of human stem cell in mesenchymal tissues such as bone marrow and dermis that can be able to differentiate into endodermal‐, ectodermal‐ and mesodermal‐lineage cells from a single cell. The cells are stress‐tolerant and can be isolated from cultured fibroblasts or bone marrow stromal cells, or directly from marrow aspirates as cells positive to SSEA‐3. They express pluripotency markers such as Nanog, Oct3/4 and Sox2, but unlike ES cells, they are non‐tumorigenic cells, a trait that is consistent with the fact that they reside in the normal tissues. We reported these cells as Muse cells (Multilineage‐differentiating stress enduring cells) in PNAS, 2010. Interestingly, in human fibroblasts, iPS cells were generated exclusively from Muse cells, but never from the non‐Muse cell population which was eliminated from Muse cells. Importantly, major factors related to pluripotency were consistently not expressed in non‐Muse cell population for the entire period. Muse cells that can be obtained through easily accessible human mesenchymal tissues will be beneficial for cell‐based therapy as well as for efficient generation of human iPS cells.