Human Mesenchymal Stem Cell-Derived Microvesicles Mitigate Aortic Smooth Muscle Cell Activation via miR-147 and Attenuate Aortic Aneurysm Formation

Objective: Mesenchymal stem cells (MSCs) can release microvesicles (MVs) but their effects on aortic aneurysm (AA) formation are unknown. We hypothesize that MSC-derived MVs can inhibit AA formation via modulation of specific microRNAs (miRs). Methods: An elastase-perfusion abdominal AA model was used with 8- to 12- week old male mice. The abdominal aorta was perfused for 5 minutes with porcine pancreatic elastase and treated with or without human umbilical cord MSC-derived MVs (1x106 given intravenously on day 1). On day14 following perfusion, the abdominal aortic diameter was measured by video micrometry and expressed as percentage increase over baseline. miRNA microarray was performed on aortic tissue using Affymetrix GeneChip hybridization. MVs were transfected with either miR-147b mimic or inhibitor (25nM, Invitrogen, CA) using Lipofectamine RNAiMAX and co-cultured with aortic smooth muscle cells (AoSMCs) followed by treatment with transient elastase (5 minutes) or recombinant IL-17 (10 ng/ml). Cytok...