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

Saijo, Hiroto, M.D.; Suzuki, Keiji, Ph.D.; Yoshimoto, Hiroshi, M.D., Ph.D.; Imamura, Yoshinobu, M.D.; Yamashita, Shunichi, M.D., Ph.D.; Tanaka, Katsumi, M.D., Ph.D.

Plastic and Reconstructive Surgery: June 2019 - Volume 143 - Issue 6 - p 1189e–1200e
doi: 10.1097/PRS.0000000000005669
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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.

Nagasaki, Japan

From the Department of Plastic and Reconstructive Surgery, Nagasaki University Graduate School of Biomedical Sciences; the Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University; and the Department of Plastic and Reconstructive Surgery, Nagasaki University Hospital.

Received for publication April 26, 2018; accepted October 10, 2018.

Disclosure:The authorshave no financial interest to declare in relation to the content of this article.

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Keiji Suzuki, Ph.D., Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 8528523, Japan, kzsuzuki@nagasaki-u.ac.jp

©2019American Society of Plastic Surgeons