title: Detection of lymphangiogenesis by near-infrared fluorescence imaging and responses to VEGF-C during healing in a mouse full-dermis thickness wound model.
abstract: Noninvasive, longitudinal near-infrared fluorescence (NIRF) imaging was used to detect and quantify lymphangiogenesis following a full-dermis thickness incision in the presence and absence of locally administered vascular endothelial growth factor-C (VEGF-C), a well-known regulator of lymphangiogenesis. Peripheral cytokines/chemokines were also measured in treated and sham-injected animals. Lymphangiogenesis was detected via NIRF imaging by day 7-8 and confirmed by intravital microscopy, while angiogenesis was observed by day 2-3 postincision (PI). All lymph vessel parameters quantified were significantly greater on wounded vs. nonwounded sides of mice. Lymph vessel parameters appeared larger on wounded sides of VEGF-C- relative to NaCl-treated mice, although differences were not significant. Interleukin-1α and interleukin-22 were significantly elevated at day 7 PI relative to respective preincision levels in VEGF-C-treated mice, and decreased by day 21 PI to levels nearing those measured preincision. For the majority of cytokines/chemokines measured, mean responses were significantly greater in VEGF-C- vs. NaCl-treated animals. Local VEGF-C administration may stimulate lymphangiogenesis during tissue repair and regeneration via mediating systemic cytokine/chemokine levels. NIRF imaging can be utilized to detect lymphangiogenesis during wound healing, and offers a promising platform to complement current methods for monitoring wound status and studying the effects of growth factors on healing.
authors.affiliation: Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas, Houston, TX 77030, USA. mary.hall@uth.tmc.edu
authors.forename: Mary A
authors.initials: MA
authors.lastname: Hall
authors.forename: Holly
authors.initials: H
authors.lastname: Robinson
authors.forename: Wenyaw
authors.initials: W
authors.lastname: Chan
authors.forename: Eva M
authors.initials: EM
authors.lastname: Sevick-Muraca
mesh_terms: D000279:Administration, Cutaneous; D043925:Angiogenesis Inducing Agents / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D018925:Chemokines / Q000276:immunology; D004396:Coloring Agents; D016207:Cytokines / Q000276:immunology; D005260:Female; D042583:Lymphangiogenesis / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D061848:Optical Imaging; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects* / Q000293:injuries; D019265:Spectroscopy, Near-Infrared; D042582:Vascular Endothelial Growth Factor C / Q000276:immunology / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology
chemical_list: D043925:Angiogenesis Inducing Agents; D018925:Chemokines; D004396:Coloring Agents; D016207:Cytokines; D011994:Recombinant Proteins; D042582:Vascular Endothelial Growth Factor C; C467483:vascular endothelial growth factor C, mouse