Boengineered Tissue Offers New Hope for Secondary Lymphedema Treatment

While these procedures are critical for cancer staging and preventing metastatic spread, they can result in severe long-term complications because lymph nodes do not naturally regenerate once removed. Their absence can cause secondary lymphedema, a condition marked by chronic swelling, discomfort, and reduced mobility that can substantially impair a patient’s quality of life. To help address this challenge, researchers now report a bioengineered lymphatic tissue designed to replace missing nodes and reestablish lymphatic flow.

Researchers at Tokyo University of Science (Tokyo, Japan) have developed a bioengineered lymphatic tissue known as CeLyT, fabricated using a centrifugal cell stacking method. In this process, mesenchymal stem cells (MSCs), selected for their regenerative support and scaffold-forming properties, are first placed into Transwell culture plate wells and centrifuged to form a uniform basal layer. Lymphatic endothelial cells are then added and centrifuged to create a second, evenly distributed layer. A final layer of MSCs, formed through an additional centrifugation step, results in a stable three-layered cellular structure.

Efficacy was evaluated in a mouse model in which the popliteal and inguinal lymph nodes of the right lower limb had been surgically removed. Following transplantation of CeLyTs, lymphatic flow was restored and the mice showed marked improvement in lymphedema symptoms with paw and leg thickness returning to normal within a few weeks of treatment. In addition, CeLyT-treated mice demonstrated recovery of filtration capacity and immune cell populations, including T cells and macrophages, along with reduced adipose tissue accumulation to levels comparable to those of healthy controls.

The researchers closely examined the structures that formed following CeLyT transplantation to better understand the observed therapeutic effects. Their post-transplant analysis indicated early formation of lymphatic and blood vessels at the graft site, followed by an immature lymph node-like structure that incorporated host-derived cells within several days. The tissue matured into a functional lymph node within 10 days after transplantation. 

The research team reports the work as the world’s first successful regeneration of fully functional lymph nodes through cell transplantation, presenting a promising therapeutic option for patients who develop lymphedema following oncologic lymph node dissection. From an economic perspective, a single transplantation may offer durable benefits, substantially reducing long-term costs associated with repeated hospital visits and prolonged use of compression garments. These findings published in Nature Communications underscore the strong curative potential of precisely bioengineered lymphatic tissue, surpassing the effectiveness of currently available treatments for lymphedema.

“Although compression therapy represents the gold standard for the treatment of lymphedema in clinical practice, it usually delays the swelling in the paws of lymphedema mice. By contrast, CeLyTs were more effective at suppressing lymphedema, also exhibiting strong therapeutic effects even in a more severe chronic lymphedema model.” said Kosuke Kusamori, Associate Professor from the Faculty of Pharmaceutical Sciences at TUS. "Moreover, CeLyTs demonstrated a greater lymphedema-suppressive effect, compared with bioengineered tissues fabricated by other tissue engineering methods."

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Tokyo University of Science