Assoc. Prof. Dr. Kosuke Kusamori

Dr. Kosuke Kusamori specializes in cellular drug discovery, biomaterial science, and advanced drug delivery systems (DDS).

Regenerative Cell-Based Therapy for Lymph Node Reconstruction

Secondary lymphedema is a chronic complication of lymph node dissection or lymphatic injury, and current treatments mainly provide symptomatic relief. Regeneration of functional lymph nodes could restore lymphatic drainage and immune surveillance, but reproducible construction of lymph node-like tissues suitable for transplantation remains a major challenge. This study aimed to develop a cell-based regenerative therapeutic platform for lymph node regeneration using centrifuge-based bioengineered lymphatic tissue (CeLyT) and to evaluate its structural and functional performance in vivo. CeLyT was fabricated by layering mesenchymal stromal cells (MSCs) and lymphatic endothelial cells (LECs) through controlled centrifugation. The engineered tissues were transplanted into a mouse lymph node excision model. Lymphatic drainage, tissue integration, immune cell organization, and local immune responses were assessed by lymphatic imaging, histology, immunostaining, and functional immune stimulation. Transplanted CeLyT promoted reconstruction of lymphatic pathways and improved lymphatic flow after lymph node excision. The grafts developed lymph node-like structures containing lymphatic vessels and organized immune cell compartments. Importantly, regenerated tissues supported lymph filtration and responded to immune stimulation, indicating recovery of key lymph node functions. Histological analysis further demonstrated integration of the transplanted tissues with surrounding host lymphatic structures and formation of functional lymphatic networks. These findings suggest that engineered lymphatic tissue composed of MSCs and LECs can provide both structural and functional components required for lymph node regeneration. This cell-based regenerative strategy enables reconstruction of functional lymph node-like tissue and may provide a curative therapeutic approach for secondary lymphedema. Further optimization of tissue fabrication and transplantation conditions will support future clinical translation.