Fig. 8

Administration of TSG-6 neutralizing antibody abrogates the therapeutic effects of MSC-CM EXO 25 wks. a-c Histogram showing BALF total cell count (a), BALF absolute neutrophil count (b), total BALF protein (c), in RA, BPD and PBS-injected, MSC-CM EXO 25 wks-injected, Isotype IgG + EXO 25 wks and NAb TSG-6 + EXO 25 wks-injected BPD mice at PN14. d Representative images of lung histology (H&E staining) from the six experimental groups, RA (I), BPD (II), BPD + PBS (III), BPD + MSC-CM EXO 25 wks (IV), BPD + Isotype IgG + EXO 25 wks (V), BPD + NAb TSG-6 + EXO 25 wks (VI). Asterisks depict the increased alveolar simplification in the BPD, PBS and NAb TSG-6 + EXO-injected BPD mice as compared to RA. ×200 magnification, Scale bar: 50 μm. e-f Histograms showing the mean chord length (e), alveolar area (f) in lungs of RA, BPD, PBS-injected, Isotype IgG + EXO 25 wks- injected and NAb TSG-6 + EXO 25 wks-injected BPD mice. g-h Histogram showing the RV to LV ratio (g) and Fulton’s index [RV/(LV + IVS)] (h), reflecting right ventricular hypertrophy at PN14. 5 μg of NAb resuspended in total 100 μl of PBS was injected into the neonatal mice at PN2 and PN4. RA, BPD, BPD + PBS and BPD + MSC-CM EXO 25 wks samples used for comparison in this analysis are from Figs. 1, 2 and 3. All values are expressed as mean ± SEM; six experiments, N = 3–8 mice per group; one-way ANOVA with Tukey’s post hoc correction; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. BALF bronchoalveolar lavage fluid, BPD bronchopulmonary dysplasia, CM conditioned medium, EXO exosomes, IVS interventricular septa, LV left ventricular, MSC mesenchymal stem cell, NAb neutralizing antibody, PBS phosphate-buffered saline, RA room air, RV right ventricular, TSG-6 tumor necrosis factor alpha-stimulated gene-6