title: Morphological and Molecular Characterization of Human Dermal Lymphatic Collectors.
abstract: Millions of patients suffer from lymphedema worldwide. Supporting the contractility of lymphatic collectors is an attractive target for pharmacological therapy of lymphedema. However, lymphatics have mostly been studied in animals, while the cellular and molecular characteristics of human lymphatic collectors are largely unknown. We studied epifascial lymphatic collectors of the thigh, which were isolated for autologous transplantations. Our immunohistological studies identify additional markers for LECs (vimentin, CCBE1). We show and confirm differences between initial and collecting lymphatics concerning the markers ESAM1, D2-40 and LYVE-1. Our transmission electron microscopic studies reveal two types of smooth muscle cells (SMCs) in the media of the collectors with dark and light cytoplasm. We observed vasa vasorum in the media of the largest collectors, as well as interstitial Cajal-like cells, which are highly ramified cells with long processes, caveolae, and lacking a basal lamina. They are in close contact with SMCs, which possess multiple caveolae at the contact sites. Immunohistologically we identified such cells with antibodies against vimentin and PDGFRα, but not CD34 and cKIT. With Next Generation Sequencing we searched for highly expressed genes in the media of lymphatic collectors, and found therapeutic targets, suitable for acceleration of lymphatic contractility, such as neuropeptide Y receptors 1, and 5; tachykinin receptors 1, and 2; purinergic receptors P2RX1, and 6, P2RY12, 13, and 14; 5-hydroxytryptamine receptors HTR2B, and 3C; and adrenoceptors α2A,B,C. Our studies represent the first comprehensive characterization of human epifascial lymphatic collectors, as a prerequisite for diagnosis and therapy.
authors.affiliation: Institute of Anatomy and Cell Biology, University Medical School Göttingen, Göttingen, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Hasselhof
authors.affiliation: Institute of Anatomy and Cell Biology, University Medical School Göttingen, Göttingen, Germany.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Sperling
authors.affiliation: Institute of Anatomy and Cell Biology, University Medical School Göttingen, Göttingen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Buttler
authors.affiliation: Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
authors.affiliation: Institute of Anatomy and Cell Biology, University Medical School Göttingen, Göttingen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Becker
authors.affiliation: Division of Trauma Surgery, Plastic and Reconstructive Surgery, University Medical Center Göttingen, Göttingen, Germany.|Center of Plastic, Hand and Reconstructive Surgery, University Medical Center Regensburg, Regensburg, Germany.
authors.forename: Thiha
authors.initials: T
authors.lastname: Aung
authors.affiliation: Division of Trauma Surgery, Plastic and Reconstructive Surgery, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Gunther
authors.initials: G
authors.lastname: Felmerer
authors.affiliation: Institute of Anatomy and Cell Biology, University Medical School Göttingen, Göttingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Wilting
mesh_terms: D001943:Breast Neoplasms / Q000098:blood supply; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042601:Lymphatic Vessels / Q000378:metabolism* / Q000473:pathology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D000067170:Telocytes / Q000378:metabolism; D013848:Thigh / Q000098:blood supply; D014746:Vimentin / Q000378:metabolism
chemical_list: D014746:Vimentin; D017479:Receptors, Platelet-Derived Growth Factor