(A) Transcriptome analysis of vehicle, cardiosphere-derived cell–treated (CDC-treated), and CDC-derived exosome–treated (EXO-treated) mdx hearts using 2-dimensional hierarchical clustering of genes with at least 1.5-fold change between WT/vehicle, CDC/vehicle, and EXO/vehicle. Both CDC and EXO treatment reversed the transcriptomic profile and partially normalized gene expression. (B) Representative NF-κB immunoblot and quantification of NF-κB phosphorylation in mdx hearts (n = 5 per group). Both CDC and EXO treatment reduced NF-κB phosphorylation. (C) Pooled data of CD68+ pixels from D reveal that CDC and EXO treatment reduces macrophage abundance (n = 6 per group). (D) Immunohistochemical staining for CD68 and α-sarcomeric actinin (α-SA) in vehicle-, CDC-, and EXO-treated mdx hearts. Scale bars: 50 μm. (E) Colorimetric analysis of protein-carbonyl adducts reveal normalization by CDC and EXO treatment (n = 7–11 per group). (F) Pooled data of Ki-67+ cardiomyocytes from F reveal that CDC and EXO treatment induces cardiomyocyte proliferation (n = 6 per group). (G) Immunohistochemical staining for Ki-67 and α-SA in vehicle-, CDC-, and EXO-treated mdx hearts. Scale bars: 50 μm. (H) Representative immunoblot of mitochondrial electron transport chain complex subunits. (I) Pooled data from H reveal that CDC and EXO treatment restores the protein levels of complexes involved in oxidative phosphorylation (OXPHOS) (n = 5–6 per group). Bar graphs depict mean ± SEM. Statistical significance was determined by ANOVA with P ≤ 0.05. When appropriate, a Newman-Keuls correction for multiple comparisons was applied. *Significantly different from WT; #significantly different from vehicle. Dashed lines in B and H represent splice sites among lanes run on the same immunoblot.