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. Author manuscript; available in PMC: 2020 Nov 26.
Published in final edited form as: ACS Nano. 2019 Sep 25;13(11):12393–12407. doi: 10.1021/acsnano.9b05115

Figure 5. Perfusion of donor heart with MMF-NP prior to transplant showed marked effect within the graft and abrogated chronic rejection.

Figure 5.

(A) H&E staining of the heart allografts at 28 days post-transplant. Control heart showed moderate to severe cellular infiltration and occluded vasculature. The heart graft perfused with free MMF showed moderate cellular infiltration and vasculopathy. The heart graft perfused with MMF-NP showed much lower cellular infiltration and intact vasculature. (B) The histological scoring of both cellular infiltration and vascular appearance showed significantly lower scores in the MMF-NP group, as compared to the control and free MMF group (control vs. free MMF vs. MMF-NP, 2.67±0.30 vs. 2.69±0.17 vs. 0.91±0.28 for cellular infiltration, 4.01±0.19 vs. 4.03±0.54 vs. 1.43±0.52 for vascular appearance score, n=4mice/group). (C) Very low infiltration of CD3+ and CD11b+ cells were observed in the heart allograft perfused with MMF-NP in comparison to control and free MMF groups. (D) Fibronectin staining showed less fibrosis in MMF-NP group compared to control and free MMF groups. (E) Gene expression of fibronectin showed significantly less expression in the allograft heart harvested from MMF-NP group compared to control and free MMF groups (control vs. free MMF vs. MMF-NP, 1.2±0.12 vs. 0.8±0.04 vs. 0.4±0.08, n=3mice/group). (F) MFI of DSA-IgG in serum from 28 days post-transplant was significantly less in MMF-NP group compared to control and free MMF groups (control vs. free MMF vs. MMF-NP, 2914±156 vs. 2532±194 vs. 2043±79, n=4mice/group). (G) Elastica van Gieson stain of the allograft heart showed thinner intima in MMF-NP group compared to control and free MMF groups (control vs. free MMF vs. MMF-NP, 42.6±8.4 vs. 17.6±4.1 vs. 6.8±2.4, 2 random arteries from each mouse, n=4mice/group). (H) Gene expression of VCAM, ICAM and P-selectin in the allograft heart showed significantly less expression in MMF-NP group compared to control (control vs. free MMF vs. MMF-NP, 1.3±0.1 vs. 1.0±0.1 vs. 0.6±0.1 for VCAM, 0.9±0.02 vs. 0.8±0.1 vs. 0.7±0.09 for ICAM, 1.2±0.1 vs. 0.8±0.08 vs. 0.6±0.06 for P-selectin n=3mice/group). (J) HUVEC cells stimulated by TNFα showed high expression of VCAM, ICAM and P-selectin, which were suppressed by adding MMF-NP to a greater degree than by free MMF (control vs. free MMF vs. MMF-NP, 13.4±1.2 vs. 10.2±0.9 vs. 8.6±0.5 for VCAM, 27.4±3.0 vs. 15.9±2.3 vs. 7.1±1.2 for ICAM, 36.8±2.1 vs. 15.7±0.9 vs. 10.7±1.2 for P-selectin n=3mice/group).