Mesenchymal Stem/Stromal Cells: ENDOGENOUS NON-TUMORIGENIC PLURIPOTENT MUSE CELLS;BASIC RESEARCH AND CLINICAL TRIALS

ABSTRACT

Background & Aim: Multilineage-differentiating stress enduring (Muse) cells, collectable as pluripotent surface marker SSEA-3-positive, are naturally existing non-tumorigenic pluripotent stem cells that distribute in the bone marrow, peripheral blood, connective tissue of every organ, and exhibit triploblastic differentiation and self-renewability at a single cell level. They are also contained in cultured MSCs and fibroblasts as several percent, and are expandable to a clinical scale. Circulating Muse cells, both endogenous and intravenously injected exogenous cells, selectively home to damaged tissue by sensing sphingosine-1-phosphate (S1P), one of the general alert signals produced by the damaged tissue, and then spontaneously differentiate into multiple tissue-constituent cells to replace damaged/ apoptotic cells. In this manner, they repair tissues. In addition, they have a specific immunomodulatory system, represented by HLA-G expression, allowing allogenic-Muse cells to directly administrate to patients without HLA-matching or long-term immunosuppressant (Figure Presented) treatment, and to remain in the host tissue as differentiated functional cells for more than half a year, as shown by animal models. Methods, Results & Conclusion: For these characteristics, intravenous drip is the main route of treatment and do not require surgery for their administration, nor do they require gene introduction or cytokine treatment to be rendered pluripotency and/or differentiation. Currently, clinical trials using intravenously administered donor- Muse cells have been conducted for myocardial infarction, stroke, epidermolysis bullosa, spinal cord injury, perinatal hypoxic ischemic encephalopathy, amyotrophic lateral sclerosis and COVID19-ARDS, all by intravenous drip of donor-derived Muse cell formula, CL2020, without HLA-matching or immunosuppressant treatment. The result of randomized, double-blind, placebo-controlled clinical trial in stroke patients confirmed safety and efficacy of Muse cell-based product for up to 52 weeks (1 year). Muse cells may safely provide beneficial effects compatible with the ‘body’s natural repair systems’ by a simple cost- effective strategy;collection, expansion and intravenous drip.