Scaffold implantation modulates the systemic immune response post-MI, and cATMSC-EV promote a local effect. (A-C) Systemic analysis of the immune response post-MI. (A) The increase in the number of total peripheral blood mononuclear cells (PBMC) (left) and specifically in the number of lymphocytes (right) in whole blood that occurs 2 days after MI (red) is prevented by scaffold implantation. (B) The increase in the number of CCR2+ monocytes observed 30 days post-MI in untreated animals is blocked by scaffold implantation. (C) EV-Treated animals reduce the expression of CD73 in circulating monocytes 30 days from MI. Bars indicate mean ± SD and each data point corresponds to one animal (n = 4;7;8 respectively). Statistical significance was calculated with a paired Two-way ANOVA with Tukey's posthoc analysis. (D-E) Representative images (D) and quantification (E) of the number of infiltrating macrophages (CD163+; left), of which expressed CD73 (middle), and cells expressing CD73 (right) by immunohistofluorescence analysis at 30 days post-MI. Statistical significance was calculated with a One-way ANOVA with Tukey's posthoc analysis (Infarct core, left) and Student T-test (Scaffold, right). (E) CD163 (red), CD73 (green) and DAPI (blue).