Fig. 10: VEGFC mRNA-LNP treatment restores lymphatic function in experimental lymphedema.
a Monitoring active lymphatic function in the contralateral hind limbs of the same tamoxifen-treated Flt4-CreERT2; iDTRfl/fl mouse 30 or 75 days after the injection of Diphtheria toxin and 1 µg of Poly(C) into one paw and Diphtheria toxin and 1 µg of VEGFC mRNA-LNPs into another paw. Poly(C) or VEGFC mRNA-LNPs were injected 8 days after Diphtheria toxin treatment. 70 kDa Rh-D was injected into the paws and the transport of the molecule was monitored by fluorescent microscopy 90 min post Rh-D administration. Representative images are shown of 5-7 mouse hind limbs in each group (bars, 1000 µm). Green rectangles show the magnified area which represent the area of popliteal lymph nodes. b Fluorescent intensity of popliteal lymph nodes of tamoxifen-treated Flt4-CreERT2; iDTRfl/fl mice 30 and 75 days after the injection of Diphtheria toxin and 1 µg of Poly(C) into one paw and Diphtheria toxin and 1 µg of VEGFC mRNA-LNPs into another paw. Poly(C) or VEGFC mRNA-LNPs were injected 8 days after Diphtheria toxin treatment. 70 kDa Rh-D was injected into the paws and the transport of the molecule was monitored by fluorescent microscopy 90 min post Rh-D administration. Quantitative data are represented as mean and SEM in 5–7 popliteal lymph nodes in each group (two-tailed, paired T-test, P = 0.0425 after 30 days for 5 mice and P = 0.0373 after 75 days for 7 mice). Asterisks indicate P < 0.05 compared with control.
