Bioengineered Tissue: A Revolutionary Step in Lymphedema Treatment
The global rise in cancer cases has led to an increase in surgeries involving lymph node removal, a procedure that can have severe long-term consequences. One such consequence is secondary lymphedema, a condition causing chronic swelling, discomfort, and reduced mobility in affected limbs or areas, significantly impacting patients' quality of life. To address this, regenerative medicine focuses on restoring or regenerating damaged lymphatic structures.
Current approaches, such as stem cell and lymphatic tissue transplantation, have shown limited success. A research team led by Associate Professor Kosuke Kusamori from the Tokyo University of Science (TUS) has developed an innovative lymphatic tissue engineering technique. Their study, published in Nature Communications, introduces a straightforward protocol for producing bioengineered lymphatic tissues that can restore lymphatic flow after lymph node removal.
The team's approach involves a novel centrifugal cell stacking technique. They start by placing mesenchymal stem cells (MSCs) in Transwell culture plate wells, forming a first layer. After centrifugation, lymphatic endothelial cells are added and spread evenly as a second layer. Another centrifugation step adds more MSCs, resulting in a three-layered cellular structure called centrifuge-based bioengineered lymphatic tissue (CeLyT).
Using a lymphedema animal model, the team successfully regenerated functional lymph nodes with structural similarity to native lymph nodes. Transplanting CeLyTs restored lymphatic flow in mice with removed popliteal and inguinal lymph nodes, leading to remarkable lymphedema symptom improvement. These mice showed normal paw and leg thickness within weeks, and their filtration capacity, immune cell populations, and adipose tissue accumulation returned to normal levels.
The researchers analyzed the structures formed after CeLyT transplantation, revealing the initial lymph and blood vessel formation, followed by the establishment of an immature lymph node-like structure. This structure matures and functions as a lymph node within 10 days after transplantation.
This study marks the world's first successful regeneration of fully functional lymph nodes through cell transplantation, offering a promising therapeutic option for lymphedema patients post-oncologic surgeries. Economically, a single transplantation could provide long-lasting benefits, reducing cumulative costs associated with repeated hospital visits and compression garment use.
Dr. Kusamori highlights CeLyTs' superior lymphedema-suppressive effect compared to compression therapy, which delays swelling in lymphedema mice. CeLyTs demonstrate strong therapeutic effects even in severe chronic lymphedema models, surpassing the efficacy of other tissue engineering methods.
The research team's findings open up exciting possibilities for translating CeLyTs into clinical practice, offering hope for a revolutionary treatment for lymphedema patients.
