Sphingosine-1-Phosphate Receptor 2 Agonist Mobilises Endogenous Muse Cells to Repair Damaged Myocardial Tissue in Male Rabbits.

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&#xa0;situ. Acute myocardial infarction (AMI) model rabbits were subcutaneously injected either with Vehicle (n&#x2009;=&#x2009;15), S1PR2-agonist (n&#x2009;=&#x2009;16), or S1PR2-agonist + S1PR2-antagonist (n&#x2009;=&#x2009;10). The number of Muse cells in the peripheral blood was assessed by flow cytometry at 12&#x2009;h after AMI. The S1PR2-agonist group showed a significant increase in the peripheral-blood Muse cell number at 12&#x2009;h (p&#x2009;<&#x2009;0.05), as well as infarct size reduction (p&#x2009;<&#x2009;0.05) and improvement of left ventricular (LV) function (p&#x2009;<&#x2009;0.05) at 2&#x2009;weeks compared with the other 2 groups. The number of peripheral-blood Muse cells positively correlated with LV ejection fraction (p&#x2009;<&#x2009;0.05) and inversely correlated with infarct size (p&#x2009;<&#x2009;0.05). Transplanted autologous green fluorescent protein (GFP)-labelled BM-Muse cells into the BM, followed by the administration of either Vehicle (n&#x2009;=&#x2009;5) or S1PR2 agonist (n&#x2009;=&#x2009;5) revealed a higher number of homed GFP-Muse cells expressing the cardiac markers troponin-I, &#x3b1;-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.