title: Optimization and regeneration kinetics of lymphatic-specific photodynamic therapy in the mouse dermis.
abstract: Lymphatic vessels transport fluid, antigens, and immune cells to the lymph nodes to orchestrate adaptive immunity and maintain peripheral tolerance. Lymphangiogenesis has been associated with inflammation, cancer metastasis, autoimmunity, tolerance and transplant rejection, and thus, targeted lymphatic ablation is a potential therapeutic strategy for treating or preventing such events. Here we define conditions that lead to specific and local closure of the lymphatic vasculature using photodynamic therapy (PDT). Lymphatic-specific PDT was performed by irradiation of the photosensitizer verteporfin that effectively accumulates within collecting lymphatic vessels after local intradermal injection. We found that anti-lymphatic PDT induced necrosis of endothelial cells and pericytes, which preceded the functional occlusion of lymphatic collectors. This was specific to lymphatic vessels at low verteporfin dose, while higher doses also affected local blood vessels. In contrast, light dose (fluence) did not affect blood vessel perfusion, but did affect regeneration time of occluded lymphatic vessels. Lymphatic vessels eventually regenerated by recanalization of blocked collectors, with a characteristic hyperplasia of peri-lymphatic smooth muscle cells. The restoration of lymphatic function occurred with minimal remodeling of non-lymphatic tissue. Thus, anti-lymphatic PDT allows control of lymphatic ablation and regeneration by alteration of light fluence and photosensitizer dose.
authors.affiliation: Institute of Bioengineering and Swiss Institute for Cancer Research (ISREC), School of Life Sciences, SV-IBI-LLCB, Station 15, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland, Witold.Kilarski@epfl.ch.
authors.forename: Witold W
authors.initials: WW
authors.lastname: Kilarski
authors.forename: Angelika
authors.initials: A
authors.lastname: Muchowicz
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Wachowska
authors.forename: Renata
authors.initials: R
authors.lastname: Mężyk-Kopeć
authors.forename: Jakub
authors.initials: J
authors.lastname: Golab
authors.forename: Melody A
authors.initials: MA
authors.lastname: Swartz
authors.forename: Patrycja
authors.initials: P
authors.lastname: Nowak-Sliwinska
mesh_terms: D055011:Ablation Techniques; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D020405:Dermis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004423:Ear / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D007700:Kinetics; D008027:Light; D042601:Lymphatic Vessels / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects / Q000528:radiation effects
chemical_list: D017319:Photosensitizing Agents
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