Hayashida Kenji, Yoshida Shuhei, Yoshimoto Hiroshi, Fujioka Masaki, Saijo Hiroto, Migita Kiyoshi, Kumaya Misato, Akita Sadanori
Nagasaki and Oita, Japan.
From the Departments of Plastic and Reconstructive Surgery and Molecular Immunology, Nagasaki University Graduate School of Biomedical Sciences; the Department of Plastic and Reconstructive Surgery, National Nagasaki Medical Center; and Oita University.
Plast Reconstr Surg. 2017 Mar;139(3):639-651. doi: 10.1097/PRS.0000000000003110.
Secondary lymphedema is often observed in postmalignancy treatment of the breast and the gynecologic organs, but effective therapies have not been established in chronic cases even with advanced physiologic operations. Currently, reconstructive surgery with novel approaches has been attempted.
The hindlimbs of 10-week-old male C57BL/6J mice, after 30-Gy x-irradiation, surgical lymph node dissection, and 5-mm gap creation, were divided into four groups, with vascularized lymph node transfer abdominal flap and 1.0 × 10 adipose-derived stem cells. Lymphatic flow assessment, a water-displacement plethysmometer paw volumetry test, tissue quantification of lymphatic vessels, and functional analysis of lymphatic vessels and nodes were performed.
Photodynamic Eye images, using indocyanine green fluorescence, demonstrated immediate staining in subiliac lymph nodes, and linear pattern imaging of the proximal region was observed with the combined treatment of adipose-derived stem cells and vascularized lymph node transfer. Both percentage improvement and percentage deterioration with the combined treatment of adipose-derived stem cells and vascularized lymph node transfer were significantly better than with other treatments (p < 0.05). The numbers of lymphatic vessels with LYVE-1 immunoreactivity significantly increased in mice treated with adipose-derived stem cells (p < 0.05), and B16 melanoma cells were metastasized in groups treated with vascularized lymph node transfers by day 28.
Adipose-derived stem cells increase the number of lymphatic vessels and vascularized lymph node transfers induce the lymphatic flow drainage to the circulatory system. Combined adipose-derived stem cell and vascularized lymph node transfer treatment in secondary lymphedema may effectively decrease edema volume and restore lymphatic function by lymphangiogenesis and the lymphatic-to-venous circulation route.
继发性淋巴水肿常见于乳腺癌和妇科器官的恶性肿瘤治疗后，但即使采用先进的生理手术，慢性病例的有效治疗方法仍未确立。目前，已尝试采用新方法进行重建手术。
对10周龄雄性C57BL/6J小鼠后肢进行30 Gy X线照射、手术淋巴结清扫及5 mm间隙创建后，分为四组，分别接受带血管蒂淋巴结转移腹部皮瓣和1.0×10脂肪来源干细胞治疗。进行淋巴流评估、排水容积法爪体积测量试验、淋巴管组织定量分析以及淋巴管和淋巴结功能分析。
使用吲哚菁绿荧光的光动力眼图像显示髂下淋巴结立即染色，脂肪来源干细胞与带血管蒂淋巴结转移联合治疗观察到近端区域的线性模式成像。脂肪来源干细胞与带血管蒂淋巴结转移联合治疗的改善百分比和恶化百分比均显著优于其他治疗（p<0.05）。脂肪来源干细胞治疗的小鼠中，LYVE-1免疫反应性淋巴管数量显著增加（p<0.05），到第28天，带血管蒂淋巴结转移治疗组出现B16黑色素瘤细胞转移。
脂肪来源干细胞增加淋巴管数量，带血管蒂淋巴结转移诱导淋巴流向循环系统引流。继发性淋巴水肿中脂肪来源干细胞与带血管蒂淋巴结转移联合治疗可能通过淋巴管生成和淋巴-静脉循环途径有效减少水肿体积并恢复淋巴功能。
