Structural reconstruction of mouse acute aortic dissection by intravenously administrated human-Muse cells without immunosuppression

Abstract

Abstract Stanford type B acute aortic dissection (Stanford-B AAD) is often fatal. Endogenous pluripotent-like Muse cells selectively home to damaged tissue via sphingosine-1-phosphate, phagocytose damaged cells to differentiate into the damaged cell type and ultimately repair the tissue. Here we show the therapeutic efficacy of a single dose (50,000 cells) intravenous injection of human Muse cells in a Stanford-B AAD mouse model without immunosuppression. Homing to the AAD tissue, on-site differentiation into aorta constituent cells, elastin production, elastic fiber reorganization, alleviation of inflammatory cell migration, mitigation of aortic diameter expansion, aortic rupture avoidance, and survival rate improvement were superior in the Muse group when compared to the human mesenchymal stem cell (750,000 cells, containing 50,000 Muse cells) group. HLA-G expression was found to be integral for protecting Muse cells from immunorejection. Therefore, a small dose of purified Muse cells might be more effective than a large dose of MSCs for AAD.