Removing Barriers to Regenerative Medicine And Promoting Innovative Applications: The Discovery Of Human Endogenous Pluripotent Muse Cells

Abstract

Multilineage-differentiating stress-enduring (Muse) cells are naturally existing, non-tumorigenic reparative endogenous stem cells identified by SSEA-3 expression. Muse cells are able to differentiate into nearly all cell types in the body, mobilize from the bone marrow to the peripheral blood and distribute to the connective tissue of organs, and contribute to daily minute repair of damaged/lost cells by spontaneous differentiation into tissue-compatible cells. Endogenous Muse cells express receptors for damage signaling by sphingosine-1-phosphate and are thus able to specifically home to sites of damage to regenerate healthy tissue by simultaneous differentiation into multiple tissue-constituent cells. When the number of endogenous Muse cells is not sufficient, administration of exogenous Muse cells delivers robust functional recovery. Muse cells do not need to be "induced" or genetically manipulated to exhibit pluripotency or to differentiate into various cell types for clinical use. Intravenous drip is the main method of administration, making surgery unnecessary. Furthermore, because Muse cells have an immunomodulatory system similar to the placenta, donor-derived Muse cells can be directly administered to patients without human leukocyte antigen-matching or immunosuppression therapy. Clinical trials for the treatment of myocardial infarction, stroke, and epidermolysis bullosa by intravenous delivery of donor-derived Muse cells are currently being conducted by the Life Science Institute Inc., a member of the Mitsubishi Chemical Holdings Corporation. Overall, Muse cells may safely provide clinically relevant regenerative effects compatible with the 'body's natural repair systems' by a simple, cost-effective strategy—collection of Muse cells, large-scale expansion, and intravenous administration.