Paracrine Effects of Adipose-Derived Stem Cells Promote Lymphangiogenesis in Irradiated Lymphatic Endothelial Cells

BACKGROUND:There is currently no reliable treatment for secondary lymphedema caused by lymph node dissection or radiotherapy; however, stem cell–based regenerative medicine is emerging as a promising remedy for such complications. The purpose of this study was to examine the effects of adipose-derived stem cells on lymphangiogenesis involving human dermal lymphatic endothelial cells exposed to ionizing radiation. METHODS:Proliferation, migration, and tube formation were analyzed in human dermal lymphatic endothelial cells that were co-cultured with adipose-derived stem cells or cultured in adipose-derived stem cell–conditioned medium. The levels of lymphangiogenic factors secreted from adipose-derived stem cells were analyzed by enzyme-linked immunosorbent assays and Western blotting. RESULTS:Co-culturing with adipose-derived stem cells and the use of adipose-derived stem cell–conditioned medium both significantly promoted proliferation, migration, and tube formation in nonirradiated human dermal lymphatic endothelial cells. The authors also found that irradiated adipose-derived stem cells had similar alleviative effects on irradiated human dermal lymphatic endothelial cells. Enzyme-linked immunosorbent assays and Western blotting analysis revealed that irradiating adipose-derived stem cells increased their secretion of basic fibroblast growth factor in a dose-dependent manner, whereas it caused no detectable change in their secretion of vascular endothelial growth factor A or C, or hepatocyte growth factor. CONCLUSIONS:These results demonstrated that factors secreted by adipose-derived stem cells contribute to the promotion of lymphangiogenesis in irradiated human dermal lymphatic endothelial cells. The authors’ findings also suggest that radiation potentiates the paracrine effects of adipose-derived stem cells by stimulating basic fibroblast growth factor protein expression.