Transplantation Surgery and ResearchAdipose-Derived Stem Cells Promote Proliferation, Migration, and Tube Formation of Lymphatic Endothelial Cells In Vitro by Secreting Lymphangiogenic FactorsTakeda, Kohsuke MD*; Sowa, Yoshihiro MD, PhD*; Nishino, Kenichi MD, PhD*; Itoh, Kyoko MD, PhD†; Fushiki, Shinji MD, PhD†Author Information From the Departments of *Surgery, Division of Plastic and Reconstructive Surgery, and †Pathology and Applied Neurobiology, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan. Received June 17, 2013, and accepted for publication, after revision, November 13, 2013. Conflicts of interest and sources of funding: none declared. Reprints: Kohsuke Takeda, MD, Department of Surgery, Division of Plastic and Reconstructive Surgery, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. E-mail: [email protected]. This study was supported by Grants-in-Aid for Challenging Exploratory Research (No. 23659834) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. Annals of Plastic Surgery: June 2015 - Volume 74 - Issue 6 - p 728-736 doi: 10.1097/SAP.0000000000000084 Buy Metrics Abstract Adipose-derived stem cells (ADSCs) are a promising new therapeutic modality for several diseases and have been applied to various clinical fields because of their multidifferentiation potential and capacity for growth-factor secretion. Recently, 2 in vivo studies showed ADSCs to have potential applications in lymphedema therapy. However, it remains unclear whether ADSCs have direct effects on lymphatic endothelial cells (LECs). In this study, human LECs were treated with murine ADSC-derived conditioned media. Changes in LEC proliferation, migration, and tube formation were assessed by WST-8 assay, transwell chamber assay, and Matrigel-based tube formation assay, respectively, with recombinant human vascular endothelial growth factor-C used as a positive control. Additionally, the expression of several lymphangiogenic factors in ADSCs was examined by quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Factors secreted by ADSCs induced LEC proliferation, migration, and tube formation more potently than recombinant human vascular endothelial growth factor-C. We confirmed by quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay that some of the lymphangiogenic factors of ADSCs were dramatically up-regulated under serum-starved conditions. These data indicate that ADSCs could directly contribute to lymphangiogenesis via secretory factors in vitro and may thus provide a therapeutic modality for patients with lymphedema. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.