Cell transplantation therapy for a rat model of secondary lymphedema

Abstract

Background: Although lymphedema is a progressive and lifelong condition, substantial advances in therapeutic intervention are limited. The development of a novel therapy for lymphedema is urgent for those patients suffering from it. The aim of this study was to investigate the usefulness of a new cell transplantation therapy in the rat tail model of secondary lymphedema.

Materials and methods: We prepared two cell sources, human dermal microvascular endothelial cells (HDMECs) and lymphatic endothelial cells (LECs), which were collected from the resected normal dermis of patients with breast cancer. After the animal model of secondary lymphedema of the nude rats' tails was established, phosphate-buffered saline, purified LECs, or unpurified HDMECs were injected in the rats' tails five times for more than 14 d. The evaluations were performed by measuring the circumference, fluorescence lymphography, and histologic analysis of the rats' tails between each group.

Results: The isolated cells by the simple immunomagnetic sorting from HDMECs were positive for a pan-endothelial marker (CD31) and lymphatic-specific markers (podoplanin, lymphatic vessel endothelial hyaluronan receptor-1 [LYVE-1], and prospero homebox 1 [Prox-1]), and were considered to be LECs. In the cell transplantation group, which was injected with human LECs, the circumference, lymphatic flow, and thickness of the skin of the rat tail became thinner than the groups injected with unpurified HDMECs or phosphate-buffered saline. Immunohistochemistry of the rat tails showed that the number of own lymphatic vessels was increased in the purified LEC transplantation group compared with the other groups. Furthermore, in the LEC transplantation group, some vessels were immunopositive for human-podoplanin or -LYVE-1 and the areas adjacent to the vessels were rat-podoplanin or -LYVE-1 immunopositive.

Conclusions: Our findings indicate that cell transplantation therapy using human LECs improved the secondary lymphedema in the nude rat tail. This therapeutic strategy may merit clinical investigation in patients with lymphedema.

Keywords: Cell transplantation; Lymphangiogenesis; Lymphatic endothelial cell; Lymphatic vessel; Secondary lymphedema.