Transplantation of Lymph Node Fragments in a Rabbit Ear Lymphedema Model: A New Method for Restoring the Lymphatic Pathway

Abstract

The treatment of lymphedema by medical or surgical means remains a difficult task, and no technique is presently satisfactory. We established a rabbit ear chronic lymphedema model in which sequential lymph node fragments were transplanted to restore lymphatic pathways. Twenty New Zealand White rabbits were divided into two groups of 10 animals. One group served as the control, and the other was the transplantation group. A 3-cm-wide strip of skin and subcutaneous tissue including all the lymphatics was excised circumferentially from the root part of the right ear in each rabbit. The vascular pedicle in the control group was wrapped with a "bridge" strip of skin from the ventral ear to protect it from drying. In the transplantation group, the auricular lymph node was harvested from the contralateral ear, cut into 1- to 2-mm slices, and implanted next to the vascular pedicle where the lymph vessels had been resected. Water displacement measurements in both groups revealed significant edema (p < 0.001) compared with the contralateral ear at 3 days. Peak swelling was observed at 10 days in both groups. Volumes decreased in both groups postoperatively. The volume measured as percentage change in the lymph node transplantation group was significantly lower than in the control group at 2 months and continuing to the end of the experiment (p < 0.001). Indirect lymphographic examination revealed that the distal lymphatic vessels of the control group were increased in number, dilated, and did not allow proximal passage of dye. Light microscopy revealed the vascular pedicle to be surrounded by dense scar tissue in the "bridge." The transplantation group showed free passage of dye through the bridge. Microscopic examination showed regenerated lymphoid tissue with sinuses along the artery and vein of the "bridge." Many channels with a layer of endothelial cells were also noted. Electron microscopy confirmed these sites to be regenerated lymph vessels. Lymphatic tissue can regenerate after fragment transplantation. This lymph tissue seems to regenerate lymphatic vessels that may function for drainage. The results suggest that this simple technique may be applicable in a clinical situation to prevent or treat obstructive lymphedema.

Extracorporeal shock wave therapy ameliorates secondary lymphedema by promoting lymphangiogenesis

“…Male Japanese white rabbits were purchased from the Oriental Yeast Company (Tokyo, Japan) and bred in the Animal Center of Yamaguchi University. The rabbit ear model of lymphedema was created as described previously 14,15,19 with minor modification. The rabbits were given general anesthesia before surgery.…”

VEGF-C gene therapy augments postnatal lymphangiogenesis and ameliorates secondary lymphedema

“…We modified several previous rabbit ear models to overcome the shortcomings of rapid lymphatic regeneration and to provide the bed for new lymphatic vessel growth (5,24,25). To meet those requirements, we used old (3-4 years of age) New Zealand White rabbits and created a skin bridge.…”

“…The ear was put in a 50-ml cylinder filled with water. After removing the ear, the volume of water displaced by the ear was measured (25). The thickness and volume of all ears was measured before surgery and every week for 6 weeks, and thereafter every 2 weeks until the 12-week point (n = 12 in each group).…”

Radiologic Manifestations of Senile Lymph Nodes in the Popliteal Fossa

“…[24][25][26] Based on results from these experiments, preliminary trials of lymph node transplantation have been attempted clinically for treating lymphedema of the upper extremities. 27,28 Procedures have included a vascularized groin free flap containing superficial inguinal lymph nodes that was harvested from the inguinal region and transferred to a recipient site (axillary, elbow, or wrist) on the affected limb for restoring lymphatic drainage function.…”