Danhong Injection Enhances the Therapeutic Efficacy of Mesenchymal Stem Cells in Myocardial Infarction by Promoting Angiogenesis

Figures

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  FIGURE 1. MSC assessment. (A) Cell surface marker of UC-MSCs at P5 showing positive for CD73, CD90, and CD105 and negative for CD19, CD11b, CD34, and CD45. (B) Morphological images of UC-MSCs at P5 (×100).

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  FIGURE 2. Effects of MSC combined with DHI on cardiac function and hemodynamics in MI mice. LV ejection fraction (A) and fractional shortening (B) of mice in each group after intervention for 14 days. (C–F) indicated LV ejection fraction (EF), fractional shortening (FS), early and late diastolic mitral flow velocity ratio (E/A), and mitral valve diastolic velocity ratio (E′/A′) in each group after 28 days of intervention, respectively. (G,H) The LV maximum upstroke velocity (+dp/dtmax) and maximum descent velocity (–dp/dtmax) were examined by cardiac catheterization. (I) Representative echocardiographic images (M-mode) in different groups. All values are means ± SD (n = 8 or n = 6). #p < 0.05, ##p < 0.01 versus model group; NS means no significant difference.

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  FIGURE 3. Pathological examination was performed by HE and Masson staining. (A,B) Representative photomicrographs of HE-stained and Masson-stained myocardium (200×). (C) Representative heart longitudinal panoramic view. (D) The infarct area ratio was quantified by midline method. (E,F) Representative percentage of heart and lung wet weight to body weight. All values are means ± SD (n = 4 or n = 8). #p < 0.05, ##p < 0.01 versus model group; NS means no significant difference.

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  FIGURE 4. Molecular imaging of Dil-MSCs retention after transplantation. (A,B) Effect of DHI on MSC retention after 7 and 14 days of transplantation. (C,D) Representative fluorescence images of mice transplanted with MSC and MSC + DHI at 7 and 14 days were obtained by IVIS. (E) Representative myocardial photomicrographs of mice after transplantation of MSC and MSC + DHI for 28 days. All values are means ± SD (n = 8). ##p < 0.01 versus model group.

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  FIGURE 5. DHI promotes the survival of MSC through the SDF-1/CXCR4 signaling pathway. Quantitative real-time PCR analysis of gene expression of SDF-1 (A), CXCR4 (B), and VEGF (C) in heart samples with various treatments. (D) The representative western blotting bands of SDF-1 and CXCR4 protein in different groups. (E) Semi-quantitative analysis of SDF-1 and CXCR4 protein were normalized against GAPDH expression. All values are means ± SD (n = 3). #p < 0.05, ##p < 0.01 versus model group; NS means no significant difference.

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  FIGURE 6. The effect of DHI main component of Danshensu on MSC cells. (A) Effect of Danshensu on the expression of CXCR4 protein in MSCs. (B) Representative flow cytometric analysis of CXCR4-PE in MSCs. (C) MSC cell migration was assessed by transwell assay under different interventions. (D) The number of MSC migration statistics. All values are means ± SD (n = 3). #p < 0.05, ##p < 0.01 versus control group; NS means no significant difference.