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

Abstract

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. 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. 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. 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.