VEGF-C gene therapy augments postnatal lymphangiogenesis and ameliorates secondary lymphedema
J. Clin. Invest. Young-sup Yoon, et al. 111:717 doi:10.1172/JCI15830 [Go to this article.]

Figure 4
(a) Gene transfer of phVEGF-C decreases lymphedema in a mouse tail model of lymphedema. Tail thickness was significantly greater in the operated tail than in the unoperated tail during the entire 5 weeks. In the VEGF-C group, compared with the saline, LacZ, and VEGF₁₆₅ groups, the tail thickness was significantly smaller at 3–5 weeks (*P < 0.05). No-op, no operation. (b–m) phVEGF-C induces lymphangiogenesis in a mouse tail model of lymphedema. (b–k) Immunohistochemistry using markers of lymphatic endothelium, LYVE-1 (b–f), and VEGFR-3 (g–k), in normal (b and g) and operated (3 weeks after lymphedema surgery) skin sections from the saline (c and h), LacZ (d and i), VEGF-C (e and j), and VEGF₁₆₅ (f and k) groups. Lymphatic vessels are seen as brown color (black arrows). Note the abundance of hyperplastic lymphatic vessels in phVEGF-C–transfected sections (e and j). l and m show quantification of LYVE-1– and VEGFR-3–positive lymphatic vessels. Compared with normal and control (saline, LacZ, and VEGF₁₆₅) groups, the VEGF-C group showed significantly higher lymphatic vessel density. *P < 0.05 vs. normal; **P < 0.01 vs. LE-saline and LE-LacZ. Scale bar, 100 μm.