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. 2019 Apr 4;4(7):e125754. doi: 10.1172/jci.insight.125754

Figure 3. Skeletal muscle improvements by systemic CDC or EXO delivery.

Figure 3

(A) In vitro force-frequency relationship of WT, vehicle-, cardiosphere-derived cell–treated (CDC-treated), or CDC-derived exosome–treated (EXO-treated) mdx solei (n = 5–8 per group). Both CDC and EXO treatment shifted the force-frequency curve up and to the left. (B) Twitch and (C) tetanic force derived from A demonstrate that CDC and EXO treatment boosts the developed force by mdx solei (n = 5–8 per group). (D) Pooled data from E reveal less interstitial fibrosis in CDC- and EXO-treated mdx solei (n = 5–6 per group). (E) Representative Masson’s trichrome–stained micrographs from vehicle-, CDC-, and EXO-treated mdx solei. Scale bars: 100 μm. (F) Pooled data from E reveal more total myofibers in CDC- and EXO-treated mdx solei (n = 5–6 per group). (G) Transcriptome analysis of vehicle-, CDC-, and EXO-treated mdx solei using 2-dimensional hierarchical clustering of genes with at least 1.5-fold change between vehicle/WT, CDC/vehicle, and EXO/vehicle. Both CDC and EXO treatment reversed the transcriptomic profile and partially normalized gene expression. (H) Representative NF-κB immunoblot and quantification of NF-κB phosphorylation in mdx solei. CDC treatment normalized NF-κB phosphorylation (n = 5 per group). In contrast, NF-κB phosphorylation was preserved by EXO treatment (n = 5 per group). (I) Immunohistochemical staining for CD68 and α-sarcomeric actinin (α-SA) in vehicle-, CDC-, EXO-treated mdx solei. Scale bars: 50 μm. (J) Pooled data from I reveal a greater abundance of CD68+ pixels in CDC- and EXO-treated mdx solei (n = 6–7 per group). (K) Immunohistochemical staining for neonatal myosin heavy chain (nMHC) and laminin in vehicle-, CDC-, and EXO-treated mdx solei. Scale bars: 50 μm. (L) Pooled data from K reveal more nMHC+ myofibers in CDC- and EXO-treated mdx solei (n = 7 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 H represent splice sites among lanes run on the same immunoblot.