Abstract

Discovery of Muse Cells shifts the Paradigm of Mesenchymal Stem Cells

Mari Dezawa, Professor and Chair, Department of Stem Cell Biology and Histology & Department of Anatomy and Anthropology, Tohoku University

We discovered non-tumorigenic pluripotent stem cells, Multilineage differentiating Stress Enduring (Muse) cells, that reside in the bone marrow (BM), adipose tissue, dermis, as well as in the connective tissue of every organ. Muse cells correspond to ~0.03% of BM-mononucleated cells and to several percent of cultured fibroblasts. Muse cells are stress-tolerant, express pluripotency markers despite low telomerase activity, and are able to self-renew and generate cells of all three germ layers from a single cell. These cells can be identified as cells positive for both SSEA-3. A unique and highly useful feature of Muse cells is their specific ability to detect damage signals, which allows them to migrate toward and home into damaged tissues when infused into the peripheral blood stream where they can spontaneously differentiate into cells compatible with the homed-into tissue. These activities were confirmed in models of fulminant hepatitis, muscle degeneration, and skin injury. These effects are not recognized in remainder of mesenchymal cells, namely non-Muse cells. The discovery of Muse cells addresses a longtime question regarding the mechanism of spontaneous recovery in the living body. Muse cells are distributed from the bone marrow to the connective tissue of every organ via the peripheral blood where they contribute to maintaining tissue homeostasis in each region. These cells are highly feasible for clinical therapy because of their non-tumorigenicity. The future of regenerative medicine will depend on the full utilization of the 'laws of nature', taking advantage of the internal regenerative potential already possessed by the living body.