Fig. 4: Administration of VEGFC mRNA-LNPs results in organ-specific effects in vivo. | Nature Communications

Fig. 4: Administration of VEGFC mRNA-LNPs results in organ-specific effects in vivo.

From: Nucleoside-modified VEGFC mRNA induces organ-specific lymphatic growth and reverses experimental lymphedema

Fig. 4

a 1 µg of Poly(C) or VEGFC mRNA-LNPs were intradermally injected into the back skin of C57Bl/6 mice. Growth of lymphatic vessels in back skin, lung, and small intestine was monitored 22 days after the injection. Representative images 22 days after the treatment of the back skin of 4 mice per group are shown by anti-LYVE1 immunostaining of slides processed by paraffin-based histology (bars, 125 µm). Arrows indicate LYVE1 positive lymphatic vessels. b 5 µg of Poly(C) or VEGFC mRNA-LNPs were intradermally injected into the ear of C57Bl/6 mice. Growth of lymphatic vessels in the injected and non-injected ears, lung, and small intestine was assessed 22 days after the injection. Representative images after the ear treatment of 4 mice per group are shown by anti-LYVE1 and anti-Podoplanin immunostaining of slides processed by paraffin-based histology (bars 125 µm). Arrows indicate LYVE1 and Podoplanin double positive lymphatic vessels. c Monitoring the effect of intradermal injection into ears of Prox1GFP mice with 5 µg of Poly(C) or VEGFC mRNA-LNPs shown by flow cytometry analysis. 5 µg of Poly(C) or VEGFC mRNA-LNPs were intradermally injected into the ear. Injected and non-injected ears, lungs, and small intestines were harvested and digested into single cell suspension. Quantitative data for GFP positive cell number are represented as mean and SEM from Poly(C) or VEGFC mRNA-LNP-injected ears, non-injected ears, non-injected lungs, and non-injected small intestines of 4 mice in VEGFC mRNA-LNP group and 3 mice in control group 22 days after mRNA-LNP injection (two-tailed, unpaired T-test for injected ears of Poly(C) RNA-LNP injected vs VEGFC mRNA-LNP injected mice P = 0.0402, two-tailed, unpaired T-test for contralateral non-injected ears of Poly(C) RNA-LNP injected vs. VEGFC mRNA-LNP injected mice P = 0.4006, two-tailed, unpaired T-test for lungs of Poly(C) RNA-LNP injected vs VEGFC mRNA-LNP injected mice P = 0.3168, two-tailed, unpaired T-test for small intestines of Poly(C) RNA-LNP injected vs VEGFC mRNA-LNP injected mice P = 0.1252). Asterisks indicate P < 0.05 compared with control. All cell nuclei are labeled with DAPI (blue) in paraffin-embedded tissues.

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