jte-013 and Myocardial-Infarction

Multilineage-differentiating stress enduring (Muse) cells, pluripotent marker stage-specific embryonic antigen-3. The main objective of this study is to clarify the efficiency of intravenously infused rabbit autograft, allograft, and xenograft (human) bone marrow-Muse cells in a rabbit acute myocardial infarction model and their mechanisms of tissue repair.. In vivo dynamics of Nano-lantern-labeled Muse cells showed preferential homing of the cells to the postinfarct heart at 3 days and 2 weeks, with ≈14.5% of injected GFP (green fluorescent protein)-Muse cells estimated to be engrafted into the heart at 3 days. The migration and homing of the Muse cells was confirmed pharmacologically (S1PR2 [sphingosine monophosphate receptor 2]-specific antagonist JTE-013 coinjection) and genetically (S1PR2-siRNA [small interfering ribonucleic acid]-introduced Muse cells) to be mediated through the S1P (sphingosine monophosphate)-S1PR2 axis. They spontaneously differentiated into cells positive for cardiac markers, such as cardiac troponin-I, sarcomeric α-actinin, and connexin-43, and vascular markers. GCaMP3 (GFP-based Ca calmodulin probe)-labeled Muse cells that engrafted into the ischemic region exhibited increased GCaMP3 fluorescence during systole and decreased fluorescence during diastole. Infarct size was reduced by ≈52%, and the ejection fraction was increased by ≈38% compared with vehicle injection at 2 months, ≈2.5 and ≈2.1 times higher, respectively, than that induced by mesenchymal stem cells. These effects were partially attenuated by the administration of. Muse cells may provide reparative effects and robust functional recovery and may, thus, provide a novel strategy for the treatment of acute myocardial infarction.

Topics: Allografts; Animals; Autografts; Cell Differentiation; Cell Movement; GATA4 Transcription Factor; Graft Survival; Green Fluorescent Proteins; Heterografts; Humans; Luciferases; Luminescent Proteins; Lysophospholipids; Male; Myocardial Infarction; Pluripotent Stem Cells; Pyrazoles; Pyridines; Rabbits; Receptors, Lysosphingolipid; Recombinant Fusion Proteins; RNA Interference; RNA, Small Interfering; Species Specificity; Sphingosine; Sphingosine-1-Phosphate Receptors