Abstract
Muse cells, pluripotent stem cells present mainly in the bone marrow (BM) selectively accumulate to damaged tissue by sensing sphingosine-1-phosphate (S1P) and replace damaged cells by differentiating in situ. Acute myocardial infarction (AMI) model rabbits were subcutaneously injected either with Vehicle (n = 15), S1PR2-agonist (n = 16), or S1PR2-agonist + S1PR2-antagonist (n = 10). The number of Muse cells in the peripheral blood was assessed by flow cytometry at 12 h after AMI. The S1PR2-agonist group showed a significant increase in the peripheral-blood Muse cell number at 12 h (p < 0.05), as well as infarct size reduction (p < 0.05) and improvement of left ventricular (LV) function (p < 0.05) at 2 weeks compared with the other 2 groups. The number of peripheral-blood Muse cells positively correlated with LV ejection fraction (p < 0.05) and inversely correlated with infarct size (p < 0.05). Transplanted autologous green fluorescent protein (GFP)-labelled BM-Muse cells into the BM, followed by the administration of either Vehicle (n = 5) or S1PR2 agonist (n = 5) revealed a higher number of homed GFP-Muse cells expressing the cardiac markers troponin-I, α-actinin, connexin-43 and the vascular marker CD31 in the border areas in the S1PR2-agonist group compared with the vehicle group. The mobilisation of endogenous Muse cells using S1PR2-agonist may be a promising therapeutic approach.