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Animal experiment protocols and echocardiography results. a) Experimental design for the intracardiac injection of EVs into an ICM rat model. b) Serial echocardiographic images of the three groups before MI, after MI, 2 weeks after administration, and 4 weeks after administration. c) Echocardiographic parameters (LVDd, LVDs, and LVEF) in the three groups before MI, after MI, 2 weeks after administration, and 4 weeks after administration. Data are presented as the mean ± SEM. Statistical analyses were performed using a mixed effect model including factors for group, time, and interaction between group and time with a post-hoc comparison using Tukey–Kramer method EF, ejection fraction; EV: extracellular vesicle; H-EVs: hypoxic EVs; ICM: ischemic cardiomyopathy; LAD: left anterior descending; MI: MI; LEW, Lewis rats; LVDs, left ventricular end-systolic diameter; LVDd, left ventricular-end diastolic diameter; LVEF: left ventricular ejection fraction; N -EVs: normoxic EVs; <t>PBS,</t> <t>phosphate-buffered</t> saline.
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Animal experiment protocols and echocardiography results. a) Experimental design for the intracardiac injection of EVs into an ICM rat model. b) Serial echocardiographic images of the three groups before MI, after MI, 2 weeks after administration, and 4 weeks after administration. c) Echocardiographic parameters (LVDd, LVDs, and LVEF) in the three groups before MI, after MI, 2 weeks after administration, and 4 weeks after administration. Data are presented as the mean ± SEM. Statistical analyses were performed using a mixed effect model including factors for group, time, and interaction between group and time with a post-hoc comparison using Tukey–Kramer method EF, ejection fraction; EV: extracellular vesicle; H-EVs: hypoxic EVs; ICM: ischemic cardiomyopathy; LAD: left anterior descending; MI: MI; LEW, Lewis rats; LVDs, left ventricular end-systolic diameter; LVDd, left ventricular-end diastolic diameter; LVEF: left ventricular ejection fraction; N -EVs: normoxic EVs; <t>PBS,</t> <t>phosphate-buffered</t> saline.
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Animal experiment protocols and echocardiography results. a) Experimental design for the intracardiac injection of EVs into an ICM rat model. b) Serial echocardiographic images of the three groups before MI, after MI, 2 weeks after administration, and 4 weeks after administration. c) Echocardiographic parameters (LVDd, LVDs, and LVEF) in the three groups before MI, after MI, 2 weeks after administration, and 4 weeks after administration. Data are presented as the mean ± SEM. Statistical analyses were performed using a mixed effect model including factors for group, time, and interaction between group and time with a post-hoc comparison using Tukey–Kramer method EF, ejection fraction; EV: extracellular vesicle; H-EVs: hypoxic EVs; ICM: ischemic cardiomyopathy; LAD: left anterior descending; MI: MI; LEW, Lewis rats; LVDs, left ventricular end-systolic diameter; LVDd, left ventricular-end diastolic diameter; LVEF: left ventricular ejection fraction; N -EVs: normoxic EVs; PBS, phosphate-buffered saline.

Journal: Regenerative Therapy

Article Title: Hypoxia conditioned adipose-derived stem cell-derived extracellular vesicle therapy improves cardiac function in a rat model of ischemic cardiomyopathy

doi: 10.1016/j.reth.2026.101105

Figure Lengend Snippet: Animal experiment protocols and echocardiography results. a) Experimental design for the intracardiac injection of EVs into an ICM rat model. b) Serial echocardiographic images of the three groups before MI, after MI, 2 weeks after administration, and 4 weeks after administration. c) Echocardiographic parameters (LVDd, LVDs, and LVEF) in the three groups before MI, after MI, 2 weeks after administration, and 4 weeks after administration. Data are presented as the mean ± SEM. Statistical analyses were performed using a mixed effect model including factors for group, time, and interaction between group and time with a post-hoc comparison using Tukey–Kramer method EF, ejection fraction; EV: extracellular vesicle; H-EVs: hypoxic EVs; ICM: ischemic cardiomyopathy; LAD: left anterior descending; MI: MI; LEW, Lewis rats; LVDs, left ventricular end-systolic diameter; LVDd, left ventricular-end diastolic diameter; LVEF: left ventricular ejection fraction; N -EVs: normoxic EVs; PBS, phosphate-buffered saline.

Article Snippet: After seeding the cryopreserved cells, they were washed twice with Dulbecco's phosphate-buffered saline (PBS; Nacalai Tesque) when they reached approximately 90% confluence.

Techniques: Injection, Comparison, Saline

Result of histological analysis . a) Representative images of LV fibrosis in the three groups. Whole LV tissues were stained with Sirius red. b) Representative images of microvascular density (CD34-positive area) in the peri-infarct zone of the ICM rat heart 14 days after treatment. c) Representative images of aortic ring assay. Sprout count was assessed on day 5 after addition of EVs to the culture medium. The VEGF concentration used as a positive control was 40 ng/mL (n = 3 in each group). Data are presented as the mean ± SEM. Statistical analyses were performed using one-way analysis of variance with post-hoc comparisons using the Tukey–Kramer method. EV: extracellular vesicle; H-EVs: hypoxic EVs; ICM: ischemic cardiomyopathy; LV, left ventricular; N -EVs: normoxic EVs; PBS, phosphate-buffered saline; VEGF: vascular endothelial growth factor.

Journal: Regenerative Therapy

Article Title: Hypoxia conditioned adipose-derived stem cell-derived extracellular vesicle therapy improves cardiac function in a rat model of ischemic cardiomyopathy

doi: 10.1016/j.reth.2026.101105

Figure Lengend Snippet: Result of histological analysis . a) Representative images of LV fibrosis in the three groups. Whole LV tissues were stained with Sirius red. b) Representative images of microvascular density (CD34-positive area) in the peri-infarct zone of the ICM rat heart 14 days after treatment. c) Representative images of aortic ring assay. Sprout count was assessed on day 5 after addition of EVs to the culture medium. The VEGF concentration used as a positive control was 40 ng/mL (n = 3 in each group). Data are presented as the mean ± SEM. Statistical analyses were performed using one-way analysis of variance with post-hoc comparisons using the Tukey–Kramer method. EV: extracellular vesicle; H-EVs: hypoxic EVs; ICM: ischemic cardiomyopathy; LV, left ventricular; N -EVs: normoxic EVs; PBS, phosphate-buffered saline; VEGF: vascular endothelial growth factor.

Article Snippet: After seeding the cryopreserved cells, they were washed twice with Dulbecco's phosphate-buffered saline (PBS; Nacalai Tesque) when they reached approximately 90% confluence.

Techniques: Staining, Aortic Ring Assay, Concentration Assay, Positive Control, Saline

RNA sequencing data of the left ventricular peri-infarct zone cardiac tissue in the rat MI model 2 days post-treatment . a) Heatmaps of genes related to cardiac regeneration and gene expression were compared between the two groups: H-EV and PBS administration. b) Heatmaps of genes related to cardiac regeneration and gene expression were compared between the two groups: H-EV and N -EV administration. c) The mechanism and reference of the genes in A and B. d) Gene set enrichment analysis (GSEA). The expression of genes related to “Interferon gamma response” was significantly increased in the N -EV-treated group and further increased in the H-EV-treated group. e) GSEA. The expression of genes related to “proinflammatory and profibrotic mediators,” “chemokine receptors bind chemokines,” and “cytokine-cytokine receptor interaction” was significantly increased in the H-EV-treated group compared with those in the N -EV-treated group. H-EVs: hypoxic extracellular vesicles; MI: MI; N -EVs: normoxic extracellular vesicles; NES: Normalized Enrichment Score; PBS: phosphate-buffered saline.

Journal: Regenerative Therapy

Article Title: Hypoxia conditioned adipose-derived stem cell-derived extracellular vesicle therapy improves cardiac function in a rat model of ischemic cardiomyopathy

doi: 10.1016/j.reth.2026.101105

Figure Lengend Snippet: RNA sequencing data of the left ventricular peri-infarct zone cardiac tissue in the rat MI model 2 days post-treatment . a) Heatmaps of genes related to cardiac regeneration and gene expression were compared between the two groups: H-EV and PBS administration. b) Heatmaps of genes related to cardiac regeneration and gene expression were compared between the two groups: H-EV and N -EV administration. c) The mechanism and reference of the genes in A and B. d) Gene set enrichment analysis (GSEA). The expression of genes related to “Interferon gamma response” was significantly increased in the N -EV-treated group and further increased in the H-EV-treated group. e) GSEA. The expression of genes related to “proinflammatory and profibrotic mediators,” “chemokine receptors bind chemokines,” and “cytokine-cytokine receptor interaction” was significantly increased in the H-EV-treated group compared with those in the N -EV-treated group. H-EVs: hypoxic extracellular vesicles; MI: MI; N -EVs: normoxic extracellular vesicles; NES: Normalized Enrichment Score; PBS: phosphate-buffered saline.

Article Snippet: After seeding the cryopreserved cells, they were washed twice with Dulbecco's phosphate-buffered saline (PBS; Nacalai Tesque) when they reached approximately 90% confluence.

Techniques: RNA Sequencing, Gene Expression, Expressing, Saline