Muse Cells Provide the Pluripotency of Mesenchymal Stem Cells: Direct Contribution of Muse Cells to Tissue Regeneration.

While mesenchymal stem cells (MSCs) are easily accessible from mesenchymal tissues, such as bone marrow and adipose tissue, they are heterogeneous, and their entire composition is not fully identified. MSCs are not only able to differentiate into osteocytes, chondrocytes, and adipocytes, which belong to the same mesodermal lineage, but they are also able to cross boundaries between mesodermal, ectodermal, and endodermal lineages, and differentiate into neuronal- and hepatocyte-like cells. However, the ratio of such differentiation is not very high, suggesting that only a subpopulation of the MSCs participates in this cross-lineage differentiation phenomenon. We have identified unique cells that we named multilineage-differentiating stress-enduring (Muse) cells that may explain the pluripotent-like properties of MSCs. Muse cells comprise a small percentage of MSCs, are able to generate cells representative of all three germ layers from a single cell, and are nontumorigenic and self-renewable. Importantly, cells other than Muse cells in MSCs do not have these pluripotent-like properties. Muse cells are particularly unique compared with other stem cells in that they efficiently migrate and integrate into damaged tissue when supplied into the bloodstream, and spontaneously differentiate into cells compatible with the homing tissue. Such a repairing action of Muse cells via intravenous injection is recognized in various tissues including the brain, liver, and skin. Therefore, unlike ESCs/iPSCs, Muse cells render induction into the target cell type prior to transplantation unnecessary. They can repair tissues in two simple steps: collection from mesenchymal tissues, such as the bone marrow, and intravenous injection. The impressive regenerative performance of these cells provides a simple, feasible strategy for treating a variety of diseases. This review details the unique characteristics of Muse cells and describes their future application for regenerative medicine.